Integrating Scientific Concerns on Antibody-Dependent Enhancement and Cross-Reactive Immunity with Cultural Contexts: A “Better Safe than Sorry” Model for Public Acceptance of Vaccination

Integrating Scientific Concerns on Antibody-Dependent Enhancement and Cross-Reactive Immunity with Cultural Contexts: A “Better Safe than Sorry” Model for Public Acceptance of Vaccination | Research Square window.SnipcartSettings = { analytics: { enabled: false } }; (function() { var accessVector = localStorage.getItem('access_vector') || ''; window.dataLayer = window.dataLayer || []; if (accessVector) { window.dataLayer.push({ user: { profile: { profileInfo: { snid: accessVector } } } }); } })(); (function(w,d,s,l,i){w[l]=w[l]||[];w[l].push({'gtm.start':new Date().getTime(),event:'gtm.js'});var f=d.getElementsByTagName(s)[0],j=d.createElement(s),dl=l!='dataLayer'?'&l='+l:'';j.async=true;j.src='https://www.googletagmanager.com/gtm.js?id='+i+dl;f.parentNode.insertBefore(j,f);})(window,document,'script','dataLayer','GTM-K279D39R'); Browse Preprints In Review Journals COVID-19 Preprints AJE Video Bytes Research Tools Research Promotion AJE Professional Editing AJE Rubriq About Preprint Platform In Review Editorial Policies Our Team Advisory Board Help Center Sign In Submit a Preprint Cite Share Download PDF Article Integrating Scientific Concerns on Antibody-Dependent Enhancement and Cross-Reactive Immunity with Cultural Contexts: A “Better Safe than Sorry” Model for Public Acceptance of Vaccination Maizatul Shazwani Mohd Rus Aznan, Yusnaini Md. Yusoff, Nur Asmadayana Hasim, and 5 more This is a preprint; it has not been peer reviewed by a journal. https://doi.org/ 10.21203/rs.3.rs-7530895/v1 This work is licensed under a CC BY 4.0 License Status: Posted Version 1 posted You are reading this latest preprint version Abstract The COVID-19 pandemic has underscored the crucial importance of vaccination; however, public acceptance in Malaysia is influenced not only by access and trust but also by cultural, religious, and scientific considerations. In the Klang Valley, a highly urbanised and demographically diverse region, vaccine uptake has been relatively high. Nonetheless, scepticism remains, particularly regarding complex immunological issues such as antibody-dependent enhancement (ADE) and cross-reactive immunity. This study seeks to inform the development of a comprehensive public acceptance model for immunisation by integrating expert insights into these scientific concerns, along with socio-cultural and religious contexts. A focus group discussion (FGD) was conducted involving nine experts in public health, immunology, and vaccine policy. The transcribed data were analyzed using Reflexive Thematic Analysis, leading to the emergence of four key themes: (1) Disentangling religious, cultural, and traditional constructs; (2) Distinguishing awareness from knowledge of scientific risks; (3) Practical applicability for public health communication and policy; and (4) Model adaptability, including potential applications for other vaccines such as HPV and dengue. This study uniquely combines the Arham Model with the Health Belief Model (HBM) to create a culturally grounded framework that acknowledges both the behavioural and immunological dimensions of vaccine acceptance. By emphasising the significance of science communication, sociocultural sensitivity, and theoretical integration, this work contributes a novel, adaptable model for guiding immunisation strategies in Malaysia, offering insights that are relevant to broader global contexts. Humanities/Cultural and media studies Social science/Cultural and media studies Humanities/Health humanities Biological sciences/Immunology Humanities/Medical humanities Social science/Social policy COVID-19 vaccine antibody-dependent enhancement (ADE) cross-reactive immunity Vaccine acceptance Science communication Figures Figure 1 Figure 2 1. Introduction Public concerns frequently centre on vaccine safety and scepticism regarding their effectiveness (Azeem et al., 2025 ). Additionally, there are persistent worries about specific immunological phenomena, such as cross-reactive immunity and antibody-dependent enhancement (ADE) (Wells et al., 2025 ; Santos-Peral et al., 2024 ). In the context of COVID-19, cross-reactive immunity refers to the immune system's ability to recognise and respond to SARS-CoV-2 based on prior exposure to similar viruses, including other coronaviruses or influenza (Eggenhuizen & Ooi, 2024 ). According to Bizimana Rukundo ( 2024 ), cross-reactive immunity is characterised by the immune system's response to a pathogen that shares antigenic structures with another pathogen. This involves the production of antibodies capable of recognising and attacking pathogens that possess similar antigenic features, even if they are not identical. While this form of cross-immunity may offer a certain degree of protection, research indicates that it is often partial, inconsistent, and insufficient for preventing severe illness. Some individuals mistakenly perceive this type of "natural" or cross-protection as sufficient, which may lead to a diminished sense of urgency or outright refusal to get vaccinated (Zheng et al., 2024 ; Jiang et al., 2024 ). This highlights the need for public health messaging that clearly communicates the stronger, more targeted, and longer-lasting protection that vaccination offers compared to the limited immunity from previous unrelated infections. In addition to cross-reactive immunity, Antibody-Dependent Enhancement (ADE) is another immunological phenomenon whereby antibodies generated from a prior infection or vaccination may inadvertently facilitate viral entry into host cells, potentially leading to more severe disease outcomes (Sun et al., 2025 ; Mese et al., 2024 ). This effect has been documented in diseases such as dengue and Zika (Lacout et al., 2024 ); however, to date, extensive trials and real-world studies have reported no evidence of ADE in individuals who received COVID-19 vaccines (Yang et al., 2025 ; Wietschel et al., 2024 ). In Malaysia, concerns surrounding ADE are particularly salient due to longstanding public debates on dengue vaccination, especially following the Dengvaxia controversy in neighbouring countries. Local experts have stressed the importance of recognising ADE risks when designing vaccination strategies, although recent position papers emphasise that newer vaccines, such as TAK-003, show no evidence of increased severity among seronegative individuals (The Sun Daily, 2024 ; The Star, 2024 ; Dengue Prevention Advocacy Malaysia, 2025 ). These experiences continue to shape public perceptions: if misinformation circulating online were to associate ADE with COVID-19 vaccines, such fears could intensify. It is therefore essential to communicate clearly, in accessible language, what ADE entails and why it is not a concern for approved COVID-19 vaccines (Peng et al., 2025 ). Understanding public perception of vaccine-related risks, such as Antibody-Dependent Enhancement (ADE) and cross-reactive immunity, requires a theoretical framework that integrates cognitive evaluation with sociocultural influences. The Health Belief Model (HBM) has traditionally served as a fundamental framework in public health, explaining individual health behaviours through constructs such as perceived susceptibility, perceived severity, perceived benefits, perceived barriers, cues to action, and self-efficacy, and has been widely applied in the context of COVID-19 vaccination (Ventonen et al., 2024 ; Limbu et al., 2022 ). However, large-scale global studies on vaccine acceptance, such as Wong et al. ( 2021 ), have primarily emphasised vaccine characteristics, including effectiveness, side effects, and country of manufacture, without explicitly applying HBM. This highlights the need for frameworks that extend beyond cognitive risk–benefit analysis alone. Nevertheless, in culturally diverse and religiously anchored societies such as Malaysia, where vaccination decisions are shaped not only by scientific reasoning but also by religious obligations and social traditions, HBM can still serve as a foundational framework, but it needs to be complemented by more inclusive approaches that reflect the sociocultural realities of the local context. To overcome these limitations, complementary frameworks that integrate cognitive, religious, and sociocultural dimensions are necessary, especially in Malaysia, where faith and cultural traditions have a significant impact on health behaviour. The Arham Model effectively highlights how religious commitment influences vaccine acceptance, indicating that aligning faith with public health values enhances the likelihood of recognising the benefits of dengue vaccination (Arham et al., 2022 ). Surprisingly, high levels of religiosity are correlated with positive attitudes towards vaccination, suggesting that faith can have a positive influence on vaccine acceptance. This insight is particularly significant for extending the model to broader immunisation challenges in Malaysia, where the general public has less understanding of complex biomedical concepts such as antibody-dependent enhancement (ADE) and cross-immunity. By embedding these scientific concerns within a framework that integrates religious and sociocultural values, future vaccine implementation strategies can be designed in ways that resonate more deeply with Malaysian society. Building on this perspective, the application of the Arham Model extends beyond dengue vaccination to encompass broader public health contexts, including COVID-19 and future vaccination programmes in Malaysia. Although the Arham Model was initially developed in relation to dengue vaccine acceptance (Arham et al., 2022 ), its focus on sociocultural and religious determinants makes it particularly relevant to COVID-19 vaccination within Malaysia’s multi-ethnic and multi-faith society. For example, concerns regarding the halal status of vaccine components or a reliance on divine protection may overshadow biomedical considerations (Kisa & Kisa, 2024 ), as highlighted in studies showing that halal labelling and religious leaders strongly shape Muslim vaccine decisions (Alsuwaidi et al., 2023 ) and that both Islamic and Western ethical perspectives support vaccination mandates for children in Malaysia (Abdullah & Yusof, 2024). By integrating the HBM with the Arham Model, this study offers a comprehensive perspective for assessing vaccine attitudes in Malaysia, effectively bridging scientific concerns with deeply rooted sociocultural values. This approach enables the development of culturally responsive health communication strategies (Ahmad et al., 2021 ; Elkalmi et al., 2021 ). Enhancing health literacy is crucial for promoting public acceptance of vaccines, particularly when addressing complex topics like Antibody-Dependent Enhancement (ADE) and cross-reactive immunity. Research demonstrates that the clear presentation of health information, which aligns with individuals' concerns, can alleviate fears and increase the willingness to receive vaccinations (Fu, 2025 ; Chandeying & Thongseiratch, 2024 ; Nowak et al., 2024 ). However, effective communication extends beyond simply providing accurate facts. Studies suggest that the delivery of these messages must resonate with the local culture, language, and beliefs of the community (Freeman et al., 2022 ; Syed Alwi et al., 2021 ). In Malaysia, where residents often seek health information from various sources, including social media, previous studies have shown that messages conveyed by trusted figures such as doctors, religious leaders, and community representatives are more effectively received (Low et al., 2025 ; Zaid et al., 2024 ; Balakrishnan et al., 2024 ). Additionally, some research cautions that the use of scientific terminology, such as ADE, without adequate explanation can cause confusion or anxiety (Chen et al., 2020 ; Limbu et al., 2022 ). Consequently, researchers agree that health messages should be straightforward, culturally relevant, and easily understandable, empowering individuals to make informed choices regarding vaccinations. Due to these ongoing challenges, there is a clear need for health communication strategies that are not only scientifically accurate but also culturally and socially relevant. Many people still misunderstand complex terms like Antibody-Dependent Enhancement (ADE) and cross-reactive immunity, which shows that more effort is needed to explain these issues clearly. Past studies often overlook the impact of knowledge, religious beliefs, cultural values, and community trust on how people respond to vaccine messages. To fill this gap, this study focuses on gathering expert views to understand better how the public interprets these risks. The primary objective is to support the development of a more comprehensive and practical model for public vaccine acceptance. This research proposes a novel and adaptable approach for shaping future immunisation strategies by integrating two established frameworks: the Health Belief Model (HBM) and the Arham Model. This new model aims to improve science communication and enhance the efficacy and public acceptance of vaccine policies. 2. Methodology This study employs an exploratory, expert-based conceptual framework approach, utilising qualitative focus group discussions (FGDs) to examine public perceptions of immunological risks, such as Antibody-Dependent Enhancement (ADE) and cross-reactive immunity, as well as how these concerns intersect with cultural and religious contexts. An exploratory design was chosen because the primary aim was not to measure prevalence, but rather to generate in-depth insights that could inform the development of a novel conceptual model of vaccine acceptance. FGDs were selected as the primary method due to their ability to foster open and interactive exchanges, enabling experts to share detailed perspectives, contextual interpretations, and real-world experiences (Amir et al., 2024 ). The format and structure of the discussions were adapted from the ethical indicators approach developed by Hasim et al. ( 2020 ; 2022 ), which promotes the use of guided yet flexible questions when exploring complex and sensitive scientific topics. Participants were purposefully selected to encompass a diverse yet complementary range of expertise in public health, immunology, bioethics, behavioural science, and vaccine policy, ensuring that the resulting model benefited from multidisciplinary insights. The focus group discussion centred around three primary areas: (i) the level of public understanding regarding antibody-dependent enhancement (ADE) and cross-reactive immunity, (ii) the impact of cultural and religious beliefs on vaccine decision-making, and (iii) the practical implications for science communication strategies and public health policy. By prioritising expert reflections, this study positions its findings as foundational contributions to a conceptual framework rather than as definitive empirical generalisations. This methodological approach fosters the integration of scientific insights with sociocultural contexts, ultimately facilitating the development of a culturally relevant and adaptable model for public acceptance of vaccination. 2.1 Participant Selection and Profile The Focus Group Discussion (FGD) took place on June 25, 2025, at the Bangi Golf Resort in Selangor, Malaysia. This venue provided a private, comfortable, and distraction-free environment that was conducive to in-depth discussions. Nine experts were purposively selected to ensure a well-rounded representation of disciplinary expertise pertinent to vaccine acceptance. Their areas of expertise encompassed public health financing, biotechnology, immunology, virology, traditional and herbal medicine, natural products, sociology of health, well-being, health informatics, renewable energy, green technology, and the sociology of science and technology. This purposive sampling strategy was employed to capture a diverse yet complementary array of perspectives across the biomedical, social science, and policy domains. Experts were chosen not only for their academic and professional credentials but also for their active participation in vaccine-related research, program implementation, or policy development. By including participants from such varied backgrounds, the FGD was able to incorporate clinical, scientific, policy, and community dimensions into the conversation. This diversity enriched the study, ensuring that the resulting conceptual framework reflected both the technical complexities of vaccine development and the socio-cultural realities of vaccine acceptance within Malaysia’s multi-ethnic context. Table 1 Participant’s Profile Participant Code Role Area of Specialisation Organization P1 Senior Assistant Director National Health Financing Ministry of Health (MOH) P2 Research Scientist Biotechnology Malaysian Genome and Vaccine Institute (MGVI) P3 Academician Cellular And Molecular Immunology, Virology, and Development of Traditional and Herbal Medicine Universiti Malaya P4 Academician Natural Products, Sociology of Health, and Well-being Universiti Kebangsaan Malaysia P5 Academician Data Science and Health Informatics Universiti Kebangsaan Malaysia P6 Academician Renewable Energy, Green Technology, Energy, and Society Universiti Kebangsaan Malaysia P7 Academician Data Science, Sociology of Health, and Biotechnology Universiti Kebangsaan Malaysia P8 Researcher Science, Technology, and Society Universiti Malaya P9 Researcher Science, Technology, and Society Universiti Malaya 2.2 Focus Group Questions To investigate professional insights into public understanding and immunological concerns surrounding COVID-19 vaccination, this study utilised a semi-structured focus group discussion (FGD) informed by a proposed conceptual framework. This framework synthesises two established behavioural models: the Health Belief Model (HBM) and the Arham Model, aiming to capture both cognitive and sociocultural aspects of vaccine decision-making. The HBM offers constructs such as perceived susceptibility, perceived severity, perceived benefits, and perceived barriers, which have been extensively applied in studies of vaccine acceptance (Wong et al., 2020 ). The Arham Model, initially designed in the context of dengue vaccination (Arham et al., 2022 ), enhances this framework by incorporating sociocultural determinants, such as religious obligations, cultural practices, and communal norms. These factors are particularly significant within Malaysia’s multi-faith and multi-ethnic society. The conceptual model depicted in Fig. 1 represents the integration of two distinct frameworks. Rooted in the Health Belief Model (HBM), it incorporates mediators such as perceived benefits and perceived risks, which capture individuals' psychological evaluations of vaccination. In contrast, the Arham Model introduces context-specific sociocultural and scientific dimensions. Key constructs, including vaccination confidence and willingness, as well as religious traditions and cultural influences, underscore the impact of belief systems and community norms on vaccine acceptance. Additionally, awareness of cross-reactive immunity and an understanding of antibody-dependent enhancement (ADE) highlight the importance of scientific knowledge in shaping perceived risks. The outcome variables in this model reflect this synthesis: attitudes toward vaccines correlate with HBM's concept of 'health motivation' and Arham's 'attitude toward the dengue vaccine,' while vaccine support aligns with HBM's 'health action' and Arham's 'intention to vaccinate.' Overall, this model offers a comprehensive framework that integrates general psychological predictors from the HBM with the sociocultural and scientific nuances emphasised in the Arham Model, aligning with the findings of Hisham et al. ( 2025 ). Building on this foundation, the study introduced two immunological constructs, awareness of ADE and knowledge of cross-reactive immunity, to capture specific scientific concerns that may shape vaccine perceptions. Their inclusion enhances the model’s ability to account for technical uncertainties that influence public confidence, thereby strengthening its relevance for health communication and vaccination policy. The integration of behavioural, sociocultural, and scientific elements also informed the design of the FGD protocol, ensuring that questions addressed not only theoretical clarity but also cultural resonance and policy applicability. This approach enabled participants to critically assess the conceptual framework and reflect on its potential contribution to effective public health messaging and immunisation strategies. The focus group discussion (FGD) lasted approximately six hours and was moderated by the principal researcher, with support from an assistant who took detailed field notes. All discussions were audio-recorded with the participants' consent and conducted in either Malay or English, depending on the individual's preference. To ensure conceptual clarity and facilitate informed dialogue, the session was organised into three stages. During the first three hours, the project leader presented the proposed conceptual model, providing participants with an overview of its theoretical foundations. This was followed by a session led by a member of the grant team, who elucidated the immunological aspects of vaccine acceptance, specifically addressing Antibody-Dependent Enhancement (ADE) and cross-reactive immunity. The final presentation was conducted by another team member, focusing on policy, ethical, and religious considerations relevant to vaccination. This staged approach promoted a shared understanding among participants, encouraged meaningful discussion, and allowed for deeper engagement with the framework, thereby enhancing the richness and saturation of the collected data. 2.3 Data Analysis All data collected from the focus group discussions, including audio recordings and observation notes, were transcribed verbatim to ensure accuracy and maintain the authenticity of participants’ contributions. Two researchers independently reviewed the transcripts to enhance reliability, improve consistency, and deepen their familiarity with the dataset, in line with the recommendations of Nyumba et al. ( 2018 ). Furthermore, the analytical approach was informed by the recent work of Hisham et al. ( 2025 ), who effectively utilised FGDs to validate an integrated model that combines the Health Belief Model (HBM) and the Arham Model in the context of vaccine acceptance. Thematic analysis was employed on the transcribed material, concentrating on recurring ideas, concerns, and perspectives regarding vaccine acceptance. Data segments were identified and coded in alignment with the indicators outlined in the proposed conceptual framework, as well as those emphasised by key stakeholders. Emergent terms, concepts, and themes were subsequently compared with existing literature to ensure their relevance and to reduce the risk of overlap or misinterpretation. This analytical process facilitated a structured and coherent framework for interpretation, thereby supporting the development of a systematically integrated dataset (Hisham et al., 2025 ; Nyumba et al., 2018 ). Coding was conducted manually by the first author and independently cross-checked by a second researcher to ensure consistency and credibility. Through this process, four overarching themes were identified: (1) Religious, Cultural, and Traditional Constructs; (2) Knowledge and Awareness; (3) Applicability for Public Health Policy; and (4) Model Adaptability and Theoretical Integration. 2.4 Ethical Approval Ethical approval for this study was granted by the University of Malaya Research Ethics Committee (UMREC) under Reference Number UM.TNC2/UMREC_4334, with approval dated 20 March 2025 and valid until March 2028. The study was conducted in accordance with the Declaration of Helsinki and the ethical guidelines established by the University of Malaya. 2.5 Informed Consent All participants provided written informed consent prior to their participation in this study. The identification and selection of suitable participants began in April 2025, followed by formal invitations sent on 13 June 2025. The focus group discussion was conducted on 25 June 2025 at the Bangi Golf Resort, Selangor, Malaysia. Each participant received an information sheet and completed a consent form before the start of the session. 3. Results This section presents the findings derived from focus group discussions (FGDs) held with experts in public health, immunology, and vaccine policy. The analysis was guided by a proposed conceptual model that integrates behavioural, sociocultural, and immunological constructs, including religious and cultural beliefs, understanding of cross-reactive immunity, awareness of Antibody-Dependent Enhancement (ADE), perceived benefits and risks, attitudes toward vaccines, and public support. Through thematic analysis, the data were meticulously examined to uncover recurring patterns, concerns, and professional insights regarding vaccine acceptance within the Malaysian context. The themes that emerged from the FGDs not only offer insights into participants’ perspectives on public understanding of these constructs but also provide constructive feedback for refining the model and informing future communication and policy strategies. Each theme is elaborated upon in detail below, supported by illustrative quotes and aligned with relevant theoretical dimensions. In this context, all participants in the Focus Group Discussion (FGD) strongly endorsed the inclusion of perceived benefits, perceived risks, attitudes toward vaccines, vaccination confidence, and willingness, as well as support for vaccines, as fundamental components of the framework. These constructs were deemed essential because they encapsulate the established pathways of the Health Belief Model (HBM) and align with the Arham Model, which has previously demonstrated that the interaction between benefits and risks is critical in shaping vaccine attitudes and intentions (Arham et al., 2022). Notably, the explicit inclusion of vaccination confidence and willingness underscores recent research emphasising that preparedness and willingness serve as vital links between attitudes and behavioural endorsement, especially in contexts characterised by uncertainty and rapid information dissemination (Betsch et al., 2018; Larson et al., 2018a). Experts highlighted that perceived benefits and risks are adequate to encapsulate the mediating processes connecting behavioural, sociocultural, and immunological factors to vaccine attitudes, readiness, and support. Consequently, the model maintains a robust theoretical foundation while ensuring conceptual clarity, illustrating how individual perceptions of advantages and disadvantages act as crucial determinants in vaccine decision-making (Rosenstock et al., 1988; Champion & Skinner, 2008; Arham et al., 2022). To further clarify this consensus, the experts indicated that the retained constructs encapsulate the essential dimensions of the Health Belief Model (HBM), thereby achieving a balance between simplicity and comprehensiveness. Specifically, perceived risks encompass elements of perceived susceptibility (an individual’s belief regarding the likelihood of contracting a condition) and perceived severity (the seriousness of its potential consequences), along with negative aspects typically categorised as perceived barriers. As a result, attitudes toward vaccines, as well as vaccination confidence and willingness and support for vaccines, integrate the motivational drivers of behaviour (the inclination to accept or utilise the vaccine), cues to action (triggers that prompt protective behaviour), and self-efficacy (the confidence in one’s ability to take effective action). This streamlined representation effectively avoids the inflation of constructs while maintaining theoretical rigour, ensuring that the model accurately reflects both the psychological appraisal processes inherent in the HBM and the sociocultural-scientific dimensions emphasised in the Arham Model. Figure 2 illustrates the model derived from the focus group discussion (FGD), showcasing the valuable insights gathered collectively. 3.1 Religious, Cultural, and Traditional From the outset of the discussion, the expert panels demonstrated strong agreement on the inclusion of religious, cultural, and traditional constructs in the proposed model. They welcomed these elements as essential, especially within Malaysia’s diverse population, where vaccine decisions are often shaped by factors beyond personal beliefs, including faith, family customs, and long-standing communal traditions (Alsuwaidi et al., 2023; Tiwana & Smith, 2024). However, what truly sparked deeper conversation was not whether these constructs belong, but how they should be represented. One of the first reflections came from a participant who pointed out that while these elements often appear side-by-side in daily life, treating them as one might confuse respondents and blur important distinctions: "Culture, tradition, and religion each have their own meaning. If we present them separately, even respondents who may not identify with religion can respond more clearly." (P4) This observation was intended as a constructive insight rather than criticism. The panellist did not dismiss the construct; instead, they expressed strong support for it. The participant was guiding the research towards a more transparent framework, asserting that the model would be significantly enhanced by acknowledging religion, culture, and tradition as distinct yet interrelated factors influencing vaccine acceptance, as outlined below: “It is important to separate the constructs for better understanding. Each element has a singular meaning: religion focuses on the spiritual, while culture and tradition emphasise how people adapt and assimilate what they learn from previous generations.” (P7) Another panellist helped bring this point to life with an everyday example. They described how certain social rituals might be misread, even by the respondents themselves, if the survey does not make a clear distinction: "For instance, consider a prayer feast for the deceased. Does it fall under culture or religion? Without a clear explanation, respondents might find it difficult to differentiate between the two. Providing such clarity can help them respond more accurately and confidently." (P6) The recommendation is clear that both the model and the formulation of questions require enhancement. Instead of assuming that respondents interpret these categories in the same way as researchers, the instruments should incorporate brief explanations or examples to aid interpretation. Such an approach not only enhances the accuracy of the data but also acknowledges the complexity of individuals' lived experiences. In some communities, cultural identity plays a more prominent role than religious affiliation, shaping everyday practices and social expectations in ways that deeply influence health behaviours (Shi et al., 2023). This is why lumping them together could lead to oversights: "In some communities, cultural practices are powerful even more so than religious beliefs. That is why we should separate them, so our questions can be more accurate." (P5) Instead of perceiving this as a challenge, the experts recognised it as an opportunity to enhance the model’s precision and relevance. By disaggregating these constructs, vaccine outreach can be more effectively tailored in the future. Religious messages could be conveyed through trusted faith leaders, while cultural norms might be addressed by community elders or during traditional events. This level of targeted communication is essential in public health, as a one-size-fits-all approach often fails to address the needs of diverse populations. One panellist further underscored this point by noting the importance of acknowledging the distinct weight of these influences in shaping vaccine attitudes: " Religion is often the first reference point for many people, but culture and tradition carry their own authority that cannot be ignored ." (P7) This insight underscores the complex reality of Malaysian society, where individuals navigate intertwined systems of meaning when making health decisions. It reinforces the notion that a singular framework would oversimplify these variations, potentially misrepresenting respondents' true motivations. Furthermore, recognising these parallel yet distinct domains enables researchers to craft survey items that more accurately represent the decision-making processes of diverse demographic groups. By the conclusion of the discussion, it became evident that the panel not only endorsed the inclusion of these constructs but also regarded their differentiation as a vital refinement. Their insights reaffirm the conceptual trajectory of the proposed model and enhance its practical significance. By recognising that religion, culture, and tradition each hold distinct roles in influencing public attitudes, this research presents a more culturally informed and communicatively effective framework for fostering vaccine trust across diverse communities. Building on these reflections, the panel strongly recommended that religiosity, traditions, and culture be treated as distinct yet interrelated constructs, rather than collapsed into a single category. Such disaggregation not only provides greater conceptual clarity but also allows researchers and policymakers to identify which of these factors exerts the most decisive influence in different community settings, thereby enhancing both the theoretical robustness and the practical applicability of the model. 3.2 Knowledge & Awareness In discussing the behavioural and cognitive constructs included in the proposed model, the experts were quick to agree that knowledge plays a pivotal role in shaping a person’s decision to receive the COVID-19 vaccine . In their view, what the public truly knows, especially about complex immunological terms like Antibody-Dependent Enhancement (ADE) and cross-reactive immunity, often determines how confident they feel in accepting or rejecting vaccination. However, they also emphasised the importance of distinguishing this construct from awareness, which they described as a more superficial form of recognition. In Malaysia’s diverse information landscape, where people are exposed to health messages through various channels, this distinction becomes crucial not only theoretically but also practically, for both measurement and public health strategy (Md Norman & Mohamad Nasir, 2025; Perumal et al., 2024; Nen & Hamzah, 2023). The panel clarified that awareness pertains to exposure—the capacity to recall having seen or heard something. Conversely, knowledge signifies a deeper level of understanding, including the ability to explain or apply a concept. One participant noted that survey design can obscure this distinction if not approached with care. “If we explain first, respondents might answer based on what they just read. That is not real knowledge.” (P4) This reflection drew nods from other participants, who believed that pre-survey definitions , while meant to help, may unintentionally influence responses and inflate knowledge scores. Another expert suggested that merging the two constructs could compromise the validity of the findings: “I believe we should separate awareness and knowledge. They are two different constructs and require properly designed questions.” (P1) The concern extended beyond mere semantics. The experts expressed a firm belief that assessing both layers, first by determining whether respondents had heard of ADE or cross-reactive immunity (awareness), and then by asking them to explain or apply these concepts (knowledge), would yield a more accurate and comprehensive understanding of public awareness. One panellist elaborated further. “Respondents may answer based on new information they just read, not what they already knew. That could affect the results.” (P3) As the conversation deepened, the panel began offering suggestions on how to strengthen the model. They proposed that questions be divided into two tiers, with awareness as the first tier , followed by knowledge, so that researchers could identify exactly where the gaps lie. “I suggest using two levels, one for awareness, and another for deeper knowledge. That way, we can clearly see where the gaps are.” (P5) Another participant noted how this method could be beneficial when assessing technical terms: “If we are going to ask about ADE or cross-reactive immunity, we must make sure people understand the meaning first. Otherwise, they will just guess.” (P2) By the end of the session, the experts fully supported the decision to keep both constructs in the model, provided they are clearly distinguished in both theory and measurement. Their feedback directly strengthens the proposed model, which aims to assess not just what people are exposed to, but what they genuinely understand. This two-layered approach, which involves awareness followed by knowledge, provides a more transparent lens for public health communicators and researchers to design more targeted education campaigns that not only inform but also truly empower. Importantly, awareness and knowledge are crucial when addressing complex issues such as antibody-dependent enhancement (ADE) and cross-reactive immunity, as these concepts significantly influence how the public perceives vaccine safety and effectiveness. 3.3 Applicability of the Model for Public Health Policy and Trust & Governance The discussion revealed that the model’s novelty lies in its ability to integrate behavioural, cultural, and governance dimensions, making it both a theoretical and operational tool. As the discussion evolved toward practical applications, the expert panel smoothly transitioned from critique to collaboration. There was a strong and shared belief that the proposed conceptual model, depicted in Figure 1, offers significant potential beyond its academic merit. The experts collectively acknowledged that the model transcends a mere diagram or theoretical framework; it can be transformed into a strategic tool for guiding public health decisions, particularly in the realms of vaccine communication, addressing public hesitancy, and enhancing trust in governance structures, including transparency, ethical compliance, and institutional credibility. What stood out in their responses was a belief that the model’s strength lies in its layered structure, which combines knowledge, sociocultural beliefs, risk perception, and behavioural support. In the words of one expert: "This model could help the Ministry of Health (KKM) identify communities that are hesitant about vaccines." (P3) This perspective resonated deeply with other panellists, who felt that Malaysia’s rich diversity requires more than a one-size-fits-all communication strategy . They believed that the model could help map patterns of concern , allowing policymakers to pinpoint who needs what kind of messaging, whether it is scientific explanation, religious reassurance, or culturally relevant storytelling. One participant reflected on the practicality of the model’s framework: "If we know which communities have higher risk or lower understanding, we can develop more targeted interventions." (P4) Another participant built on this by suggesting that the model’s utility goes beyond COVID-19, noting its flexibility for long-term use : "For long-term intervention, we could adapt this model for other vaccines too." (P2) This initiated a broader conversation regarding its future adaptability. Panellists proposed that the same framework could be applied to campaigns for HPV, dengue, or even potential future pandemics, as long as the constructs are regularly updated to reflect evolving scientific and cultural landscapes. One participant suggested that the model could serve as a monitoring tool, revisited annually to evaluate public sentiment. "This model could work like a GPS; we use it to track where public thinking is headed and adjust our route when needed." (P1) This analogy sparked further ideas about how the model could be operationalised on the ground. Another panellist emphasised the importance of training communicators and frontliners using the framework to ensure the message delivery was just as effective as the message content: "If this model is to be used in the field, health workers must be trained to understand what each construct means." (P3) Panel 9 strongly affirmed that the successful implementation of the model depends on a firm commitment to transparency and accountability within the institutions involved. "Any model will only work if the public feels that the government is honest and consistent in its communication." (P9) This reflection highlights that the effectiveness of a model is not solely determined by its technical design; it also significantly depends on the implementation of trust-building measures at the policy level. Without credible and transparent institutions, even a well-structured framework may fail to gain public confidence, making it challenging to influence behaviour. Furthermore, it emphasises the strong interconnection between governance and health communication, underscoring that the acceptance of policies primarily relies on the public's perception of fairness, consistency, and sincerity in government actions. By the end of the session, it became evident that the experts regarded the model not as a static entity, but as a dynamic, evolving tool. They valued its potential to connect academic research with the operational realities on the ground. Most importantly, they recognised that it honours the cultural, religious, and emotional dimensions often overlooked in public health planning, while also underscoring that trust in government and health institutions is a crucial factor for policy effectiveness. Their feedback underscores the model's originality and significance, not only as a conceptual contribution but also as a potential framework for translating evidence into action precisely where it matters most. This reinforces the model's applicability to public health policy and aligns with previous studies highlighting the necessity of integrating sociocultural, religious, and behavioural aspects into vaccine communication strategies (Tiwana & Smith, 2024; Dhaliwal et al., 2024; Danmaisoro & Eledi, 2024). Similar to the models used in COVID-19 vaccine campaigns and HPV vaccination programs, this framework illustrates how academic insights can be applied to inform national interventions, thereby enhancing their relevance for both current and future vaccination challenges. 3.4 Future Adaptability, Digital Health Literacy, and Strategic Use As the discussion transitioned to its final theme, the focus naturally shifted toward the future. The expert panel expressed optimism regarding the proposed model's potential to evolve, adapt, and serve beyond the immediate challenges posed by COVID-19. Initially conceived as a conceptual tool to analyse vaccine perceptions during the pandemic, they believed that this model was well-positioned to emerge as a versatile framework for long-term public health planning. The panel highlighted the model's layered structure, which integrates sociocultural, behavioural, and immunological constructs, describing it as "modular" and "future-proof." This approach provides a blueprint that can be effectively repurposed for various vaccination campaigns, targeting seasonal influenza, HPV, or emerging health threats yet to be identified. One panellist expressed appreciation for the model’s adaptability but encouraged theoretical reinforcement to enhance its credibility and utility: "We can use this model for HPV or influenza vaccines too, but it should be strengthened with theories like the Health Belief Model." (P4) The concept struck a chord with others, who recognised the significant potential in aligning the model with established behavioural frameworks, such as the Health Belief Model (HBM) and other models related to vaccine acceptance. They argued that these frameworks could offer a more robust foundation for understanding public decision-making by incorporating factors such as perceived risks, trust in the system, and the accessibility of information. "To understand why people accept or reject vaccines, we also need to consider their trust and how they interact with technology." (P6) Another participant proposed integrating digital health literacy and communication channels into the model to reflect current realities, where health information spreads rapidly both accurately and otherwise online: "I suggest including digital literacy as part of the model too." (P8) This prompted a deeper consideration of how practitioners could utilise the model in practical settings. The experts envisioned its concepts not only guiding surveys and academic publications but also being integrated into training programs for healthcare workers, risk communication strategies, and national vaccine education initiatives. "If we want to apply this model practically, we must also think about who will deliver the message, and how." (P1) Notably, the panel also suggested building feedback loops into the model’s design, allowing it to evolve as more data becomes available or as societal norms shift: "This model should be updated in line with social changes. It should not be static; it should stay dynamic and relevant." (P2) By the end of the conversation, it was evident that the panel viewed the proposed model not as a final product, but as a living framework capable of being refined, expanded, and applied across various public health contexts. Its core value, they agreed, lies in its cultural sensitivity, theoretical flexibility, and practical usability. In their view, the model’s greatest strength is its potential to serve as a bridge connecting what experts know with how communities live, believe, and decide. This underscores the model’s future adaptability and strategic use, echoing previous research which highlights the importance of flexible, theory-informed frameworks in addressing vaccine hesitancy and guiding long-term health strategies (Betsch et al., 2018; Larson, 2018b). In particular, embedding digital health literacy ensures resilience against misinformation, while the inclusion of trust and governance highlights the critical role of institutional legitimacy in sustaining vaccine confidence.Similar to approaches used in studies on influenza, HPV, and dengue vaccination campaigns, the integration of behavioural theory, sociocultural insights, and digital literacy has been shown to enhance both the reach and effectiveness of public health interventions (Hornsey et al., 2018; Nagyova, 2024; Mancone et al., 2024). Thus, the proposed model aligns with and extends existing scholarship, positioning it as a valuable tool for shaping responsive and inclusive vaccine policies in the years to come. 4. Discussion This study provides nuanced insights into the interplay of sociocultural, behavioural, and immunological factors that influence vaccine perceptions in a multi-ethnic and multi-faith society. By utilising a conceptual framework that integrates elements from the Health Belief Model (HBM) and the Arham Model, while also introducing scientifically specific constructs such as awareness of Antibody-Dependent Enhancement (ADE) and understanding of cross-reactive immunity, the research fosters a multidimensional perspective on vaccine acceptance. The findings not only affirm but also extend prior research by revealing that vaccine hesitancy in Malaysia is influenced not just by individual risk perceptions or access to healthcare, but also by deeply rooted social norms, religious beliefs, and cognitive interpretations of scientific phenomena (Balakrishnan et al., 2024; Marzo et al., 2023; Lee et al., 2023). A significant contribution of this study is its clear disaggregation of religious, cultural, and traditional constructs, a methodological choice that has been supported by robust feedback from expert participants. Previous literature frequently treated these elements as interchangeable or overlapping, which risks oversimplifying their distinct influences on public behaviour (Ngcobo & Zhandire, 2025; Kitayama & Salvador, 2024). Our findings, which align with those of Begum et al. (2024), reveal that religious frameworks often dictate vaccine permissibility, particularly in relation to halal status and the concept of divine protection. Conversely, cultural norms shape intergenerational dialogues surrounding medical interventions, while traditional practices may either reinforce or challenge biomedical recommendations. For example, cultural events or family rituals might serve as venues for either support or resistance to vaccination, depending on community-specific interpretations. This aligns with the perspectives of Ali Sheikhi et al. (2025), who contend that targeted communication through religious leaders and cultural gatekeepers significantly enhances vaccine uptake. By structurally separating these elements, the proposed model facilitates a more precise identification of drivers of hesitancy and enables communication strategies that are not only context-sensitive but also tailored to specific constructs. Furthermore, the study highlights the importance of distinguishing between awareness and knowledge, a distinction that has become increasingly crucial in discussions surrounding vaccine literacy. Awareness involves recognition and recall, while knowledge encompasses factual understanding and the capacity to apply information appropriately in context (Silva & Siscoe, 2025; Wong et al., 2022; Fernández-Fernández, 2021; Silva, 2021). Numerous studies have indicated that during the COVID-19 pandemic, a high level of awareness without a corresponding depth of knowledge rendered populations more susceptible to misinformation, particularly concerning complex immunological topics such as Antibody-Dependent Enhancement (ADE) and cross-reactive immunity (Marzo et al., 2022). In this study, experts expressed concern about the potential inflation of knowledge scores when respondents receive explanations during the survey (Abdelrahman et al., 2022). This apprehension is consistent with earlier critiques by Park and Kim (2021) regarding the construct validity of health literacy tools. The model’s two-tiered measurement design, separating recognition (awareness) from understanding (knowledge), facilitates more accurate detection of cognitive gaps. This granularity is essential for designing layered health communication interventions, whereby surface-level exposure can be followed up with more in-depth educational content, tailored to specific audience profiles. Such an approach resonates with the WHO’s (2022) call for audience segmentation in vaccine messaging, ensuring that the content not only informs but also resonates cognitively and emotionally with the public. Beyond theoretical alignment, the model was endorsed by experts for its policy utility, particularly for its capacity to guide intervention design in real-world contexts. The structure was seen as robust yet adaptable, capable of identifying patterns of vaccine hesitancy at community and national levels. These findings parallel existing literature suggesting that models incorporating sociocultural and behavioural constructs can enhance predictive accuracy in public health strategies (Lee et al., 2023). In the Malaysian context, this is particularly relevant given the prior success of culturally framed HPV and influenza vaccine campaigns (Wong et al., 2021). The expert panel specifically noted that the proposed model could support targeted risk communication, resource allocation, and prioritisation of high-hesitancy zones, consistent with WHO's strategic framework for COVID-19 vaccine deployment (WHO, 2022). The model's adaptability across various disease contexts was further highlighted by participants, who recognised its potential utility in upcoming vaccination initiatives that span from emerging infectious diseases to routine immunisation programs. This observation aligns with the broader trend in public health frameworks towards modular and scalable models that can be adjusted to meet evolving epidemiological demands (Limbu et al., 2022; Freeman et al., 2022). A key recommendation from the expert group was to enhance the theoretical robustness of the model by incorporating established behavioural models, in addition to the Health Belief Model and the Arham Model. This integration would help account for the increasingly significant roles of digital health information systems, online trust, and social media influence. Empirical evidence supports this suggestion, indicating that digital trust and eHealth literacy are critical predictors of vaccine confidence among tech-savvy populations (Ashfield et al., 2024; Bíró et al., 2023). Additionally, the call to embed digital literacy as a formal construct within the model addresses an important emerging dimension of vaccine communication. As shown in a recent cross-national study by Wells et al. (2025), misinformation thrives in the absence of digital critical thinking skills, particularly when scientific terminology (e.g., "antibody-dependent enhancement") is misunderstood or misused. Integrating such components into the model ensures its relevance within the digital communication ecosystem while allowing for longitudinal adaptability as new platforms and health technologies emerge. In conclusion, the four themes identified: religious, cultural, and traditional constructs; the distinction between awareness and knowledge; policy applicability with an emphasis on trust and governance; and future adaptability, particularly concerning Digital Health Literacy, form the foundation of the refined model presented in Figure 2. This model effectively integrates scientific concepts, such as antibody-dependent enhancement (ADE) and cross-reactive immunity, with sociocultural sensitivities to provide a comprehensive understanding of vaccine acceptance. By evolving from the conceptual framework in Figure 1 to the empirically informed model in Figure 2, the study demonstrates how theoretical insights can be transformed into a culturally grounded framework for practical applications. Importantly, the refined model embodies a “better safe than sorry” approach to public acceptance of vaccination, ensuring that immunisation strategies are not only scientifically robust but also socially resonant across diverse ethnic and faith communities. 5. Conclusion This study offers valuable insights into how expert perspectives shape the public's understanding of immunological risks, particularly regarding Antibody-Dependent Enhancement (ADE) and cross-reactive immunity in the context of COVID-19 vaccination in Malaysia. Through thematic analysis of focus group discussions, the findings highlight the necessity of distinguishing between various constructs such as religion, culture, and tradition, as well as between awareness and knowledge, each of which plays a unique role in shaping vaccine acceptance. The experts endorsed the proposed integrated model, which combines the Health Belief Model (HBM), the Arham Model, and novel scientific constructs, as a flexible and contextually relevant tool for guiding vaccine communication and public health policy. Their recommendations to incorporate digital literacy and behavioural theory further enhance the model’s adaptability across diverse populations and future immunisation initiatives. Ultimately, this research achieves its goal by presenting a comprehensive and culturally grounded model of public acceptance that can inform science communication, address vaccine hesitancy, and support evidence-based immunisation strategies in Malaysia and beyond. Declarations Acknowledgement The research was funded by the Ministry of Higher Education (MOHE), grant number CITRA-2024-003, and Universiti Kebangsaan Malaysia for its support of this research. Funding This study was supported by the CITRA-2024-003 grant from the Ministry ofHigher Education (MOHE), Malaysia. The funder provided funding to conduct surveys related to this research. Still, it did not have a significant role in the study design, data collection and analysis, the decision to publish, or the preparation of the manuscript. Contributions Ahmad Firdhaus Arham, Nurhafiza Zainal, Mohd Istajib Mokhtar, and Chin Kim Ling conceptualised the study and supervised the project. Maizatul Shazwani Mohd Rus Aznan, Yusnaini Md Yusoff, Nur Asmadayana Hasim, Noor Sharizad Rusly, and Ahmad Firdhaus Arham prepared the original draft, developed the methodology, validated the findings, and conducted the formal analysis. Maizatul Shazwani Mohd Rus Aznan, Nur Asmadayana Hasim, and Ahmad Firdhaus Arham reviewed and edited the manuscript. Ahmad Firdhaus Arham acquired funding and conducted the final review of the study. Corresponding authors Correspondence to Ahmad Firdhaus Arham and Nur Asmadayana Hasim. Competing interests The authors declare no competing interests. Ethical Approval Ethical approval for this study was obtained from the University of Malaya Research Ethics Committee (UMREC) under Reference Number UM.TNC2/UMREC_4334, approved on 20 March 2025 (valid until March 2028). Informed Consent Written informed consent was obtained from all participants. Participant selection began in April 2025, invitations were sent on 13 June 2025, and the FGD was conducted on 25 June 2025 at the Bangi Golf Resort, Selangor, Malaysia. References Abdelrahman G, Wang Q, Nunes B (2022) Knowledge Tracing: A Survey. 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Hum Vaccines Immunotherapeutics 16(9):2204–2214. https://doi.org/10.1080/21645515.2020.1790279 Wong LP, Alias H, Danaee M, Ahmed J, Lachyan A, Cai CZ, Lin Y, Hu Z, Tan SY, Lu Y, Cai G, Nguyen DK, Seheli FN, Alhammadi F, Madhale MD, Atapattu M, Quazi-Bodhanya T, Mohajer S, Zimet GD, Zhao Q (2021) COVID-19 vaccination intention and vaccine characteristics influencing vaccination acceptance: a global survey of 17 countries. Infect Dis Poverty 10(1):122. https://doi.org/10.1186/s40249-021-00900-w Yang X, Tang X, Sun Y, Xi H, Peng W, Yan L, Teng W, Zang Y, Jiang C (2025) Chimeric receptor-binding domain vaccine design and sequential immunization enhanced broadly neutralizing antibody responses against COVID-19. Front Immunol 16:1543212. https://doi.org/10.3389/fimmu.2025.1543212 Zaid SNA, Kadir A, Mohd Noor A, Ahmad N, Yusoff B, Ramli MSB, A. S., et al (2024) Translation and trans-cultural adaptation to the Malay version of the COVID-19 vaccine hesitancy questionnaire among healthcare workers in Malaysia. PLoS ONE 19(4):e0302237. https://doi.org/10.1371/journal.pone.0302237 Zheng H, Wu S, Chen W, Cai S, Zhan M, Chen C, Lin J, Xie Z, Ou J, Ye W (2024) Meta-analysis of hybrid immunity to mitigate the risk of Omicron variant reinfection. Front Public Health 12:1457266. https://doi.org/10.3389/fpubh.2024.1457266 Additional Declarations No competing interests reported. Cite Share Download PDF Status: Posted Version 1 posted You are reading this latest preprint version Research Square lets you share your work early, gain feedback from the community, and start making changes to your manuscript prior to peer review in a journal. As a division of Research Square Company, we’re committed to making research communication faster, fairer, and more useful. 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Yusoff","email":"","orcid":"","institution":"Universiti Kebangsaan Malaysia","correspondingAuthor":false,"prefix":"","firstName":"Yusnaini","middleName":"Md.","lastName":"Yu","suffix":"Md."},{"id":530817211,"identity":"1009d00f-963f-458b-b3f8-2dc17ce49dfa","order_by":2,"name":"Nur Asmadayana Hasim","email":"","orcid":"","institution":"Universiti Kebangsaan Malaysia","correspondingAuthor":false,"prefix":"","firstName":"Nur","middleName":"Asmadayana","lastName":"Hasim","suffix":""},{"id":530817215,"identity":"4c7d131e-0927-4173-af72-cf20e8869483","order_by":3,"name":"Noor Sharizad Rusly","email":"","orcid":"","institution":"Universiti Kebangsaan Malaysia","correspondingAuthor":false,"prefix":"","firstName":"Noor","middleName":"Sharizad","lastName":"Rusly","suffix":""},{"id":530817218,"identity":"58c34290-ad7c-47d7-b8ab-563790c5e784","order_by":4,"name":"Mohd Istajib Mokhtar","email":"","orcid":"","institution":"Universiti 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13:03:10","extension":"xml","order_by":7,"title":"","display":"","copyAsset":false,"role":"acdc-reference","size":183243,"visible":true,"origin":"","legend":"","description":"","filename":"4ca578b3eea745409a7952c232643e181structuring.xml","url":"https://assets-eu.researchsquare.com/files/rs-7530895/v1/672d4392ef62dde6e1eb0418.xml"},{"id":93780989,"identity":"ab380460-9088-4b4a-9420-57e767dbd9eb","added_by":"auto","created_at":"2025-10-17 13:11:10","extension":"html","order_by":8,"title":"","display":"","copyAsset":false,"role":"acdc-reference","size":193643,"visible":true,"origin":"","legend":"","description":"","filename":"earlyproof.html","url":"https://assets-eu.researchsquare.com/files/rs-7530895/v1/8298b53a382cdea9d79312ee.html"},{"id":93780298,"identity":"2759f527-93ed-4038-b9d0-079426c6175c","added_by":"auto","created_at":"2025-10-17 13:03:09","extension":"jpg","order_by":1,"title":"Figure 1","display":"","copyAsset":false,"role":"figure","size":21079,"visible":true,"origin":"","legend":"\u003cp\u003e\u003cstrong\u003eProposed conceptual framework.\u003c/strong\u003e\u003c/p\u003e","description":"","filename":"1.jpg","url":"https://assets-eu.researchsquare.com/files/rs-7530895/v1/e8957b346325e7cf1bccd469.jpg"},{"id":93780299,"identity":"18284ca8-e673-46bf-9165-cb077d53cd6f","added_by":"auto","created_at":"2025-10-17 13:03:09","extension":"jpg","order_by":2,"title":"Figure 2","display":"","copyAsset":false,"role":"figure","size":27241,"visible":true,"origin":"","legend":"\u003cp\u003e\u003cstrong\u003eFramework from FGD Insights\u003c/strong\u003e\u003c/p\u003e","description":"","filename":"2.jpg","url":"https://assets-eu.researchsquare.com/files/rs-7530895/v1/b55023e3dfa08075fc7cc99b.jpg"},{"id":102355156,"identity":"60f05414-293f-42f2-a486-d08fdb43f0c2","added_by":"auto","created_at":"2026-02-10 20:24:37","extension":"pdf","order_by":0,"title":"","display":"","copyAsset":false,"role":"manuscript-pdf","size":976545,"visible":true,"origin":"","legend":"","description":"","filename":"manuscript.pdf","url":"https://assets-eu.researchsquare.com/files/rs-7530895/v1/4e2ca863-a9c0-49ae-a8ce-93526f901909.pdf"}],"financialInterests":"No competing interests reported.","formattedTitle":"Integrating Scientific Concerns on Antibody-Dependent Enhancement and Cross-Reactive Immunity with Cultural Contexts: A “Better Safe than Sorry” Model for Public Acceptance of Vaccination","fulltext":[{"header":"1. Introduction","content":"\u003cp\u003ePublic concerns frequently centre on vaccine safety and scepticism regarding their effectiveness (Azeem et al., \u003cspan citationid=\"CR8\" class=\"CitationRef\"\u003e2025\u003c/span\u003e). Additionally, there are persistent worries about specific immunological phenomena, such as cross-reactive immunity and antibody-dependent enhancement (ADE) (Wells et al., \u003cspan citationid=\"CR62\" class=\"CitationRef\"\u003e2025\u003c/span\u003e; Santos-Peral et al., \u003cspan citationid=\"CR52\" class=\"CitationRef\"\u003e2024\u003c/span\u003e). In the context of COVID-19, cross-reactive immunity refers to the immune system's ability to recognise and respond to SARS-CoV-2 based on prior exposure to similar viruses, including other coronaviruses or influenza (Eggenhuizen \u0026amp; Ooi, \u003cspan citationid=\"CR20\" class=\"CitationRef\"\u003e2024\u003c/span\u003e). According to Bizimana Rukundo (\u003cspan citationid=\"CR13\" class=\"CitationRef\"\u003e2024\u003c/span\u003e), cross-reactive immunity is characterised by the immune system's response to a pathogen that shares antigenic structures with another pathogen. This involves the production of antibodies capable of recognising and attacking pathogens that possess similar antigenic features, even if they are not identical. While this form of cross-immunity may offer a certain degree of protection, research indicates that it is often partial, inconsistent, and insufficient for preventing severe illness. Some individuals mistakenly perceive this type of \"natural\" or cross-protection as sufficient, which may lead to a diminished sense of urgency or outright refusal to get vaccinated (Zheng et al., \u003cspan citationid=\"CR68\" class=\"CitationRef\"\u003e2024\u003c/span\u003e; Jiang et al., \u003cspan citationid=\"CR29\" class=\"CitationRef\"\u003e2024\u003c/span\u003e). This highlights the need for public health messaging that clearly communicates the stronger, more targeted, and longer-lasting protection that vaccination offers compared to the limited immunity from previous unrelated infections.\u003c/p\u003e\u003cp\u003eIn addition to cross-reactive immunity, Antibody-Dependent Enhancement (ADE) is another immunological phenomenon whereby antibodies generated from a prior infection or vaccination may inadvertently facilitate viral entry into host cells, potentially leading to more severe disease outcomes (Sun et al., \u003cspan citationid=\"CR56\" class=\"CitationRef\"\u003e2025\u003c/span\u003e; Mese et al., \u003cspan citationid=\"CR42\" class=\"CitationRef\"\u003e2024\u003c/span\u003e). This effect has been documented in diseases such as dengue and Zika (Lacout et al., \u003cspan citationid=\"CR32\" class=\"CitationRef\"\u003e2024\u003c/span\u003e); however, to date, extensive trials and real-world studies have reported no evidence of ADE in individuals who received COVID-19 vaccines (Yang et al., \u003cspan citationid=\"CR66\" class=\"CitationRef\"\u003e2025\u003c/span\u003e; Wietschel et al., \u003cspan citationid=\"CR63\" class=\"CitationRef\"\u003e2024\u003c/span\u003e). In Malaysia, concerns surrounding ADE are particularly salient due to longstanding public debates on dengue vaccination, especially following the Dengvaxia controversy in neighbouring countries. Local experts have stressed the importance of recognising ADE risks when designing vaccination strategies, although recent position papers emphasise that newer vaccines, such as TAK-003, show no evidence of increased severity among seronegative individuals (The Sun Daily, \u003cspan citationid=\"CR59\" class=\"CitationRef\"\u003e2024\u003c/span\u003e; The Star, \u003cspan citationid=\"CR58\" class=\"CitationRef\"\u003e2024\u003c/span\u003e; Dengue Prevention Advocacy Malaysia, \u003cspan citationid=\"CR19\" class=\"CitationRef\"\u003e2025\u003c/span\u003e). These experiences continue to shape public perceptions: if misinformation circulating online were to associate ADE with COVID-19 vaccines, such fears could intensify. It is therefore essential to communicate clearly, in accessible language, what ADE entails and why it is not a concern for approved COVID-19 vaccines (Peng et al., \u003cspan citationid=\"CR49\" class=\"CitationRef\"\u003e2025\u003c/span\u003e).\u003c/p\u003e\u003cp\u003eUnderstanding public perception of vaccine-related risks, such as Antibody-Dependent Enhancement (ADE) and cross-reactive immunity, requires a theoretical framework that integrates cognitive evaluation with sociocultural influences. The Health Belief Model (HBM) has traditionally served as a fundamental framework in public health, explaining individual health behaviours through constructs such as perceived susceptibility, perceived severity, perceived benefits, perceived barriers, cues to action, and self-efficacy, and has been widely applied in the context of COVID-19 vaccination (Ventonen et al., \u003cspan citationid=\"CR61\" class=\"CitationRef\"\u003e2024\u003c/span\u003e; Limbu et al., \u003cspan citationid=\"CR36\" class=\"CitationRef\"\u003e2022\u003c/span\u003e). However, large-scale global studies on vaccine acceptance, such as Wong et al. (\u003cspan citationid=\"CR65\" class=\"CitationRef\"\u003e2021\u003c/span\u003e), have primarily emphasised vaccine characteristics, including effectiveness, side effects, and country of manufacture, without explicitly applying HBM. This highlights the need for frameworks that extend beyond cognitive risk\u0026ndash;benefit analysis alone. Nevertheless, in culturally diverse and religiously anchored societies such as Malaysia, where vaccination decisions are shaped not only by scientific reasoning but also by religious obligations and social traditions, HBM can still serve as a foundational framework, but it needs to be complemented by more inclusive approaches that reflect the sociocultural realities of the local context.\u003c/p\u003e\u003cp\u003eTo overcome these limitations, complementary frameworks that integrate cognitive, religious, and sociocultural dimensions are necessary, especially in Malaysia, where faith and cultural traditions have a significant impact on health behaviour. The Arham Model effectively highlights how religious commitment influences vaccine acceptance, indicating that aligning faith with public health values enhances the likelihood of recognising the benefits of dengue vaccination (Arham et al., \u003cspan citationid=\"CR6\" class=\"CitationRef\"\u003e2022\u003c/span\u003e). Surprisingly, high levels of religiosity are correlated with positive attitudes towards vaccination, suggesting that faith can have a positive influence on vaccine acceptance. This insight is particularly significant for extending the model to broader immunisation challenges in Malaysia, where the general public has less understanding of complex biomedical concepts such as antibody-dependent enhancement (ADE) and cross-immunity. By embedding these scientific concerns within a framework that integrates religious and sociocultural values, future vaccine implementation strategies can be designed in ways that resonate more deeply with Malaysian society. Building on this perspective, the application of the Arham Model extends beyond dengue vaccination to encompass broader public health contexts, including COVID-19 and future vaccination programmes in Malaysia.\u003c/p\u003e\u003cp\u003eAlthough the Arham Model was initially developed in relation to dengue vaccine acceptance (Arham et al., \u003cspan citationid=\"CR6\" class=\"CitationRef\"\u003e2022\u003c/span\u003e), its focus on sociocultural and religious determinants makes it particularly relevant to COVID-19 vaccination within Malaysia\u0026rsquo;s multi-ethnic and multi-faith society. For example, concerns regarding the halal status of vaccine components or a reliance on divine protection may overshadow biomedical considerations (Kisa \u0026amp; Kisa, \u003cspan citationid=\"CR30\" class=\"CitationRef\"\u003e2024\u003c/span\u003e), as highlighted in studies showing that halal labelling and religious leaders strongly shape Muslim vaccine decisions (Alsuwaidi et al., \u003cspan citationid=\"CR4\" class=\"CitationRef\"\u003e2023\u003c/span\u003e) and that both Islamic and Western ethical perspectives support vaccination mandates for children in Malaysia (Abdullah \u0026amp; Yusof, 2024). By integrating the HBM with the Arham Model, this study offers a comprehensive perspective for assessing vaccine attitudes in Malaysia, effectively bridging scientific concerns with deeply rooted sociocultural values. This approach enables the development of culturally responsive health communication strategies (Ahmad et al., \u003cspan citationid=\"CR2\" class=\"CitationRef\"\u003e2021\u003c/span\u003e; Elkalmi et al., \u003cspan citationid=\"CR21\" class=\"CitationRef\"\u003e2021\u003c/span\u003e).\u003c/p\u003e\u003cp\u003eEnhancing health literacy is crucial for promoting public acceptance of vaccines, particularly when addressing complex topics like Antibody-Dependent Enhancement (ADE) and cross-reactive immunity. Research demonstrates that the clear presentation of health information, which aligns with individuals' concerns, can alleviate fears and increase the willingness to receive vaccinations (Fu, \u003cspan citationid=\"CR24\" class=\"CitationRef\"\u003e2025\u003c/span\u003e; Chandeying \u0026amp; Thongseiratch, \u003cspan citationid=\"CR15\" class=\"CitationRef\"\u003e2024\u003c/span\u003e; Nowak et al., \u003cspan citationid=\"CR46\" class=\"CitationRef\"\u003e2024\u003c/span\u003e). However, effective communication extends beyond simply providing accurate facts. Studies suggest that the delivery of these messages must resonate with the local culture, language, and beliefs of the community (Freeman et al., \u003cspan citationid=\"CR23\" class=\"CitationRef\"\u003e2022\u003c/span\u003e; Syed Alwi et al., \u003cspan citationid=\"CR57\" class=\"CitationRef\"\u003e2021\u003c/span\u003e).\u003c/p\u003e\u003cp\u003eIn Malaysia, where residents often seek health information from various sources, including social media, previous studies have shown that messages conveyed by trusted figures such as doctors, religious leaders, and community representatives are more effectively received (Low et al., \u003cspan citationid=\"CR37\" class=\"CitationRef\"\u003e2025\u003c/span\u003e; Zaid et al., \u003cspan citationid=\"CR67\" class=\"CitationRef\"\u003e2024\u003c/span\u003e; Balakrishnan et al., \u003cspan citationid=\"CR9\" class=\"CitationRef\"\u003e2024\u003c/span\u003e). Additionally, some research cautions that the use of scientific terminology, such as ADE, without adequate explanation can cause confusion or anxiety (Chen et al., \u003cspan citationid=\"CR16\" class=\"CitationRef\"\u003e2020\u003c/span\u003e; Limbu et al., \u003cspan citationid=\"CR36\" class=\"CitationRef\"\u003e2022\u003c/span\u003e). Consequently, researchers agree that health messages should be straightforward, culturally relevant, and easily understandable, empowering individuals to make informed choices regarding vaccinations.\u003c/p\u003e\u003cp\u003eDue to these ongoing challenges, there is a clear need for health communication strategies that are not only scientifically accurate but also culturally and socially relevant. Many people still misunderstand complex terms like Antibody-Dependent Enhancement (ADE) and cross-reactive immunity, which shows that more effort is needed to explain these issues clearly. Past studies often overlook the impact of knowledge, religious beliefs, cultural values, and community trust on how people respond to vaccine messages. To fill this gap, this study focuses on gathering expert views to understand better how the public interprets these risks. The primary objective is to support the development of a more comprehensive and practical model for public vaccine acceptance. This research proposes a novel and adaptable approach for shaping future immunisation strategies by integrating two established frameworks: the Health Belief Model (HBM) and the Arham Model. This new model aims to improve science communication and enhance the efficacy and public acceptance of vaccine policies.\u003c/p\u003e"},{"header":"2. Methodology","content":"\u003cp\u003eThis study employs an exploratory, expert-based conceptual framework approach, utilising qualitative focus group discussions (FGDs) to examine public perceptions of immunological risks, such as Antibody-Dependent Enhancement (ADE) and cross-reactive immunity, as well as how these concerns intersect with cultural and religious contexts. An exploratory design was chosen because the primary aim was not to measure prevalence, but rather to generate in-depth insights that could inform the development of a novel conceptual model of vaccine acceptance.\u003c/p\u003e\u003cp\u003eFGDs were selected as the primary method due to their ability to foster open and interactive exchanges, enabling experts to share detailed perspectives, contextual interpretations, and real-world experiences (Amir et al., \u003cspan citationid=\"CR5\" class=\"CitationRef\"\u003e2024\u003c/span\u003e). The format and structure of the discussions were adapted from the ethical indicators approach developed by Hasim et al. (\u003cspan citationid=\"CR25\" class=\"CitationRef\"\u003e2020\u003c/span\u003e; \u003cspan citationid=\"CR26\" class=\"CitationRef\"\u003e2022\u003c/span\u003e), which promotes the use of guided yet flexible questions when exploring complex and sensitive scientific topics.\u003c/p\u003e\u003cp\u003eParticipants were purposefully selected to encompass a diverse yet complementary range of expertise in public health, immunology, bioethics, behavioural science, and vaccine policy, ensuring that the resulting model benefited from multidisciplinary insights. The focus group discussion centred around three primary areas: (i) the level of public understanding regarding antibody-dependent enhancement (ADE) and cross-reactive immunity, (ii) the impact of cultural and religious beliefs on vaccine decision-making, and (iii) the practical implications for science communication strategies and public health policy.\u003c/p\u003e\u003cp\u003eBy prioritising expert reflections, this study positions its findings as foundational contributions to a conceptual framework rather than as definitive empirical generalisations. This methodological approach fosters the integration of scientific insights with sociocultural contexts, ultimately facilitating the development of a culturally relevant and adaptable model for public acceptance of vaccination.\u003c/p\u003e\u003cdiv id=\"Sec3\" class=\"Section2\"\u003e\u003ch2\u003e2.1 Participant Selection and Profile\u003c/h2\u003e\u003cp\u003eThe Focus Group Discussion (FGD) took place on June 25, 2025, at the Bangi Golf Resort in Selangor, Malaysia. This venue provided a private, comfortable, and distraction-free environment that was conducive to in-depth discussions. Nine experts were purposively selected to ensure a well-rounded representation of disciplinary expertise pertinent to vaccine acceptance. Their areas of expertise encompassed public health financing, biotechnology, immunology, virology, traditional and herbal medicine, natural products, sociology of health, well-being, health informatics, renewable energy, green technology, and the sociology of science and technology.\u003c/p\u003e\u003cp\u003eThis purposive sampling strategy was employed to capture a diverse yet complementary array of perspectives across the biomedical, social science, and policy domains. Experts were chosen not only for their academic and professional credentials but also for their active participation in vaccine-related research, program implementation, or policy development. By including participants from such varied backgrounds, the FGD was able to incorporate clinical, scientific, policy, and community dimensions into the conversation. This diversity enriched the study, ensuring that the resulting conceptual framework reflected both the technical complexities of vaccine development and the socio-cultural realities of vaccine acceptance within Malaysia\u0026rsquo;s multi-ethnic context.\u003c/p\u003e\u003cp\u003e\u003cdiv class=\"gridtable\"\u003e\u003ctable float=\"Yes\" id=\"Tab1\" border=\"1\"\u003e\u003ccaption language=\"En\"\u003e\u003cdiv class=\"CaptionNumber\"\u003eTable 1\u003c/div\u003e\u003cdiv class=\"CaptionContent\"\u003e\u003cp\u003eParticipant\u0026rsquo;s Profile\u003c/p\u003e\u003c/div\u003e\u003c/caption\u003e\u003ccolgroup cols=\"4\"\u003e\u003cdiv align=\"left\" class=\"colspec\" colname=\"c1\" colnum=\"1\"\u003e\u003c/div\u003e\u003cdiv align=\"left\" class=\"colspec\" colname=\"c2\" colnum=\"2\"\u003e\u003c/div\u003e\u003cdiv align=\"left\" class=\"colspec\" colname=\"c3\" colnum=\"3\"\u003e\u003c/div\u003e\u003cdiv align=\"left\" class=\"colspec\" colname=\"c4\" colnum=\"4\"\u003e\u003c/div\u003e\u003cthead\u003e\u003ctr\u003e\u003cth align=\"left\" colname=\"c1\"\u003e\u003cp\u003eParticipant Code\u003c/p\u003e\u003c/th\u003e\u003cth align=\"left\" colname=\"c2\"\u003e\u003cp\u003eRole\u003c/p\u003e\u003c/th\u003e\u003cth align=\"left\" colname=\"c3\"\u003e\u003cp\u003eArea of Specialisation\u003c/p\u003e\u003c/th\u003e\u003cth align=\"left\" colname=\"c4\"\u003e\u003cp\u003eOrganization\u003c/p\u003e\u003c/th\u003e\u003c/tr\u003e\u003c/thead\u003e\u003ctbody\u003e\u003ctr\u003e\u003ctd align=\"left\" colname=\"c1\"\u003e\u003cp\u003eP1\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c2\"\u003e\u003cp\u003eSenior Assistant Director\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c3\"\u003e\u003cp\u003eNational Health Financing\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c4\"\u003e\u003cp\u003eMinistry of Health (MOH)\u003c/p\u003e\u003c/td\u003e\u003c/tr\u003e\u003ctr\u003e\u003ctd align=\"left\" colname=\"c1\"\u003e\u003cp\u003eP2\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c2\"\u003e\u003cp\u003eResearch Scientist\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c3\"\u003e\u003cp\u003eBiotechnology\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c4\"\u003e\u003cp\u003eMalaysian Genome and Vaccine Institute (MGVI)\u003c/p\u003e\u003c/td\u003e\u003c/tr\u003e\u003ctr\u003e\u003ctd align=\"left\" colname=\"c1\"\u003e\u003cp\u003eP3\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c2\"\u003e\u003cp\u003eAcademician\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c3\"\u003e\u003cp\u003eCellular And Molecular Immunology, Virology, and Development of Traditional and Herbal Medicine\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c4\"\u003e\u003cp\u003eUniversiti Malaya\u003c/p\u003e\u003c/td\u003e\u003c/tr\u003e\u003ctr\u003e\u003ctd align=\"left\" colname=\"c1\"\u003e\u003cp\u003eP4\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c2\"\u003e\u003cp\u003eAcademician\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c3\"\u003e\u003cp\u003eNatural Products, Sociology of Health, and Well-being\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c4\"\u003e\u003cp\u003eUniversiti Kebangsaan Malaysia\u003c/p\u003e\u003c/td\u003e\u003c/tr\u003e\u003ctr\u003e\u003ctd align=\"left\" colname=\"c1\"\u003e\u003cp\u003eP5\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c2\"\u003e\u003cp\u003eAcademician\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c3\"\u003e\u003cp\u003eData Science and Health Informatics\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c4\"\u003e\u003cp\u003eUniversiti Kebangsaan Malaysia\u003c/p\u003e\u003c/td\u003e\u003c/tr\u003e\u003ctr\u003e\u003ctd align=\"left\" colname=\"c1\"\u003e\u003cp\u003eP6\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c2\"\u003e\u003cp\u003eAcademician\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c3\"\u003e\u003cp\u003eRenewable Energy, Green Technology, Energy, and Society\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c4\"\u003e\u003cp\u003eUniversiti Kebangsaan Malaysia\u003c/p\u003e\u003c/td\u003e\u003c/tr\u003e\u003ctr\u003e\u003ctd align=\"left\" colname=\"c1\"\u003e\u003cp\u003eP7\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c2\"\u003e\u003cp\u003eAcademician\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c3\"\u003e\u003cp\u003eData Science, Sociology of Health, and Biotechnology\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c4\"\u003e\u003cp\u003eUniversiti Kebangsaan Malaysia\u003c/p\u003e\u003c/td\u003e\u003c/tr\u003e\u003ctr\u003e\u003ctd align=\"left\" colname=\"c1\"\u003e\u003cp\u003eP8\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c2\"\u003e\u003cp\u003eResearcher\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c3\"\u003e\u003cp\u003eScience, Technology, and Society\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c4\"\u003e\u003cp\u003eUniversiti Malaya\u003c/p\u003e\u003c/td\u003e\u003c/tr\u003e\u003ctr\u003e\u003ctd align=\"left\" colname=\"c1\"\u003e\u003cp\u003eP9\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c2\"\u003e\u003cp\u003eResearcher\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c3\"\u003e\u003cp\u003eScience, Technology, and Society\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c4\"\u003e\u003cp\u003eUniversiti Malaya\u003c/p\u003e\u003c/td\u003e\u003c/tr\u003e\u003c/tbody\u003e\u003c/colgroup\u003e\u003c/table\u003e\u003c/div\u003e\u003c/p\u003e\u003c/div\u003e\u003cdiv id=\"Sec4\" class=\"Section2\"\u003e\u003ch2\u003e2.2 Focus Group Questions\u003c/h2\u003e\u003cp\u003eTo investigate professional insights into public understanding and immunological concerns surrounding COVID-19 vaccination, this study utilised a semi-structured focus group discussion (FGD) informed by a proposed conceptual framework. This framework synthesises two established behavioural models: the Health Belief Model (HBM) and the Arham Model, aiming to capture both cognitive and sociocultural aspects of vaccine decision-making. The HBM offers constructs such as perceived susceptibility, perceived severity, perceived benefits, and perceived barriers, which have been extensively applied in studies of vaccine acceptance (Wong et al., \u003cspan citationid=\"CR64\" class=\"CitationRef\"\u003e2020\u003c/span\u003e). The Arham Model, initially designed in the context of dengue vaccination (Arham et al., \u003cspan citationid=\"CR6\" class=\"CitationRef\"\u003e2022\u003c/span\u003e), enhances this framework by incorporating sociocultural determinants, such as religious obligations, cultural practices, and communal norms. These factors are particularly significant within Malaysia\u0026rsquo;s multi-faith and multi-ethnic society.\u003c/p\u003e\u003cp\u003eThe conceptual model depicted in Fig.\u0026nbsp;\u003cspan refid=\"Fig1\" class=\"InternalRef\"\u003e1\u003c/span\u003e represents the integration of two distinct frameworks. Rooted in the Health Belief Model (HBM), it incorporates mediators such as perceived benefits and perceived risks, which capture individuals' psychological evaluations of vaccination. In contrast, the Arham Model introduces context-specific sociocultural and scientific dimensions. Key constructs, including vaccination confidence and willingness, as well as religious traditions and cultural influences, underscore the impact of belief systems and community norms on vaccine acceptance. Additionally, awareness of cross-reactive immunity and an understanding of antibody-dependent enhancement (ADE) highlight the importance of scientific knowledge in shaping perceived risks. The outcome variables in this model reflect this synthesis: attitudes toward vaccines correlate with HBM's concept of 'health motivation' and Arham's 'attitude toward the dengue vaccine,' while vaccine support aligns with HBM's 'health action' and Arham's 'intention to vaccinate.' Overall, this model offers a comprehensive framework that integrates general psychological predictors from the HBM with the sociocultural and scientific nuances emphasised in the Arham Model, aligning with the findings of Hisham et al. (\u003cspan citationid=\"CR27\" class=\"CitationRef\"\u003e2025\u003c/span\u003e).\u003c/p\u003e\u003cp\u003eBuilding on this foundation, the study introduced two immunological constructs, awareness of ADE and knowledge of cross-reactive immunity, to capture specific scientific concerns that may shape vaccine perceptions. Their inclusion enhances the model\u0026rsquo;s ability to account for technical uncertainties that influence public confidence, thereby strengthening its relevance for health communication and vaccination policy. The integration of behavioural, sociocultural, and scientific elements also informed the design of the FGD protocol, ensuring that questions addressed not only theoretical clarity but also cultural resonance and policy applicability. This approach enabled participants to critically assess the conceptual framework and reflect on its potential contribution to effective public health messaging and immunisation strategies.\u003c/p\u003e\u003cp\u003eThe focus group discussion (FGD) lasted approximately six hours and was moderated by the principal researcher, with support from an assistant who took detailed field notes. All discussions were audio-recorded with the participants' consent and conducted in either Malay or English, depending on the individual's preference. To ensure conceptual clarity and facilitate informed dialogue, the session was organised into three stages. During the first three hours, the project leader presented the proposed conceptual model, providing participants with an overview of its theoretical foundations. This was followed by a session led by a member of the grant team, who elucidated the immunological aspects of vaccine acceptance, specifically addressing Antibody-Dependent Enhancement (ADE) and cross-reactive immunity. The final presentation was conducted by another team member, focusing on policy, ethical, and religious considerations relevant to vaccination. This staged approach promoted a shared understanding among participants, encouraged meaningful discussion, and allowed for deeper engagement with the framework, thereby enhancing the richness and saturation of the collected data.\u003c/p\u003e\u003c/div\u003e\u003cdiv id=\"Sec5\" class=\"Section2\"\u003e\u003ch2\u003e2.3 Data Analysis\u003c/h2\u003e\u003cp\u003e All data collected from the focus group discussions, including audio recordings and observation notes, were transcribed verbatim to ensure accuracy and maintain the authenticity of participants\u0026rsquo; contributions. Two researchers independently reviewed the transcripts to enhance reliability, improve consistency, and deepen their familiarity with the dataset, in line with the recommendations of Nyumba et al. (\u003cspan citationid=\"CR47\" class=\"CitationRef\"\u003e2018\u003c/span\u003e). Furthermore, the analytical approach was informed by the recent work of Hisham et al. (\u003cspan citationid=\"CR27\" class=\"CitationRef\"\u003e2025\u003c/span\u003e), who effectively utilised FGDs to validate an integrated model that combines the Health Belief Model (HBM) and the Arham Model in the context of vaccine acceptance.\u003c/p\u003e\u003cp\u003eThematic analysis was employed on the transcribed material, concentrating on recurring ideas, concerns, and perspectives regarding vaccine acceptance. Data segments were identified and coded in alignment with the indicators outlined in the proposed conceptual framework, as well as those emphasised by key stakeholders. Emergent terms, concepts, and themes were subsequently compared with existing literature to ensure their relevance and to reduce the risk of overlap or misinterpretation. This analytical process facilitated a structured and coherent framework for interpretation, thereby supporting the development of a systematically integrated dataset (Hisham et al., \u003cspan citationid=\"CR27\" class=\"CitationRef\"\u003e2025\u003c/span\u003e; Nyumba et al., \u003cspan citationid=\"CR47\" class=\"CitationRef\"\u003e2018\u003c/span\u003e).\u003c/p\u003e\u003cp\u003eCoding was conducted manually by the first author and independently cross-checked by a second researcher to ensure consistency and credibility. Through this process, four overarching themes were identified: (1) Religious, Cultural, and Traditional Constructs; (2) Knowledge and Awareness; (3) Applicability for Public Health Policy; and (4) Model Adaptability and Theoretical Integration.\u003c/p\u003e\u003c/div\u003e\n\u003ch2\u003e2.4 Ethical Approval\u003c/h2\u003e\n\u003cp\u003eEthical approval for this study was granted by the University of Malaya Research Ethics Committee (UMREC) under Reference Number UM.TNC2/UMREC_4334, with approval dated 20 March 2025 and valid until March 2028. The study was conducted in accordance with the Declaration of Helsinki and the ethical guidelines established by the University of Malaya.\u003c/p\u003e\n\u003ch2\u003e2.5 Informed Consent\u003c/h2\u003e\n\u003cp\u003eAll participants provided written informed consent prior to their participation in this study. The identification and selection of suitable participants began in April 2025, followed by formal invitations sent on 13 June 2025. The focus group discussion was conducted on 25 June 2025 at the Bangi Golf Resort, Selangor, Malaysia. Each participant received an information sheet and completed a consent form before the start of the session.\u003c/p\u003e"},{"header":"3. Results","content":"\u003cp\u003eThis section presents the findings derived from focus group discussions (FGDs) held with experts in public health, immunology, and vaccine policy. The analysis was guided by a proposed conceptual model that integrates behavioural, sociocultural, and immunological constructs, including religious and cultural beliefs, understanding of cross-reactive immunity, awareness of Antibody-Dependent Enhancement (ADE), perceived benefits and risks, attitudes toward vaccines, and public support. Through thematic analysis, the data were meticulously examined to uncover recurring patterns, concerns, and professional insights regarding vaccine acceptance within the Malaysian context. The themes that emerged from the FGDs not only offer insights into participants\u0026rsquo; perspectives on public understanding of these constructs but also provide constructive feedback for refining the model and informing future communication and policy strategies. Each theme is elaborated upon in detail below, supported by illustrative quotes and aligned with relevant theoretical dimensions.\u003c/p\u003e\n\u003cp\u003eIn this context, all participants in the Focus Group Discussion (FGD) strongly endorsed the inclusion of perceived benefits, perceived risks, attitudes toward vaccines, vaccination confidence, and willingness, as well as support for vaccines, as fundamental components of the framework. These constructs were deemed essential because they encapsulate the established pathways of the Health Belief Model (HBM) and align with the Arham Model, which has previously demonstrated that the interaction between benefits and risks is critical in shaping vaccine attitudes and intentions (Arham et al., 2022). Notably, the explicit inclusion of vaccination confidence and willingness underscores recent research emphasising that preparedness and willingness serve as vital links between attitudes and behavioural endorsement, especially in contexts characterised by uncertainty and rapid information dissemination (Betsch et al., 2018; Larson et al., 2018a). Experts highlighted that perceived benefits and risks are adequate to encapsulate the mediating processes connecting behavioural, sociocultural, and immunological factors to vaccine attitudes, readiness, and support. Consequently, the model maintains a robust theoretical foundation while ensuring conceptual clarity, illustrating how individual perceptions of advantages and disadvantages act as crucial determinants in vaccine decision-making (Rosenstock et al., 1988; Champion \u0026amp; Skinner, 2008; Arham et al., 2022).\u003c/p\u003e\n\u003cp\u003eTo further clarify this consensus, the experts indicated that the retained constructs encapsulate the essential dimensions of the Health Belief Model (HBM), thereby achieving a balance between simplicity and comprehensiveness. Specifically, perceived risks encompass elements of perceived susceptibility (an individual\u0026rsquo;s belief regarding the likelihood of contracting a condition) and perceived severity (the seriousness of its potential consequences), along with negative aspects typically categorised as perceived barriers. As a result, attitudes toward vaccines, as well as vaccination confidence and willingness and support for vaccines, integrate the motivational drivers of behaviour (the inclination to accept or utilise the vaccine), cues to action (triggers that prompt protective behaviour), and self-efficacy (the confidence in one\u0026rsquo;s ability to take effective action). This streamlined representation effectively avoids the inflation of constructs while maintaining theoretical rigour, ensuring that the model accurately reflects both the psychological appraisal processes inherent in the HBM and the sociocultural-scientific dimensions emphasised in the Arham Model. Figure 2 illustrates the model derived from the focus group discussion (FGD), showcasing the valuable insights gathered collectively.\u003c/p\u003e\n\u003cp\u003e\u003cstrong\u003e3.1 Religious, Cultural, and Traditional\u0026nbsp;\u003c/strong\u003e\u003c/p\u003e\n\u003cp\u003eFrom the outset of the discussion, the expert panels demonstrated strong agreement on the inclusion of religious, cultural, and traditional constructs in the proposed model. They welcomed these elements as essential, especially within Malaysia\u0026rsquo;s diverse population, where vaccine decisions are often shaped by factors beyond personal beliefs, including faith, family customs, and long-standing communal traditions (Alsuwaidi et al., 2023; Tiwana \u0026amp; Smith, 2024). However, what truly sparked deeper conversation was not whether these constructs belong, but how they should be represented.\u003c/p\u003e\n\u003cp\u003eOne of the first reflections came from a participant who pointed out that while these elements often appear side-by-side in daily life, treating them as one might confuse respondents and blur important distinctions:\u003c/p\u003e\n\u003cp\u003e\u003cem\u003e\u0026quot;Culture, tradition, and religion each have their own meaning. If we present them separately, even respondents who may not identify with religion can respond more clearly.\u0026quot; (P4)\u003c/em\u003e\u003c/p\u003e\n\u003cp\u003eThis observation was intended as a constructive insight rather than criticism. The panellist did not dismiss the construct; instead, they expressed strong support for it. The participant was guiding the research towards a more transparent framework, asserting that the model would be significantly enhanced by acknowledging religion, culture, and tradition as distinct yet interrelated factors influencing vaccine acceptance, as outlined below:\u003c/p\u003e\n\u003cp\u003e\u003cem\u003e\u0026ldquo;It is important to separate the constructs for better understanding. Each element has a singular meaning: religion focuses on the spiritual, while culture and tradition emphasise how people adapt and assimilate what they learn from previous generations.\u0026rdquo;\u003c/em\u003e (P7)\u003c/p\u003e\n\u003cp\u003eAnother panellist helped bring this point to life with an everyday example. They described how certain social rituals might be misread, even by the respondents themselves, if the survey does not make a clear distinction:\u003c/p\u003e\n\u003cp\u003e\u003cem\u003e\u0026quot;For instance, consider a prayer feast for the deceased. Does it fall under culture or religion? Without a clear explanation, respondents might find it difficult to differentiate between the two. Providing such clarity can help them respond more accurately and confidently.\u0026quot;\u0026nbsp;\u003c/em\u003e(P6)\u003c/p\u003e\n\u003cp\u003eThe recommendation is clear that both the model and the formulation of questions require enhancement. Instead of assuming that respondents interpret these categories in the same way as researchers, the instruments should incorporate brief explanations or examples to aid interpretation. Such an approach not only enhances the accuracy of the data but also acknowledges the complexity of individuals\u0026apos; lived experiences.\u003c/p\u003e\n\u003cp\u003eIn some communities, cultural identity plays a more prominent role than religious affiliation, shaping everyday practices and social expectations in ways that deeply influence health behaviours (Shi et al., 2023). This is why lumping them together could lead to oversights:\u003c/p\u003e\n\u003cp\u003e\u003cem\u003e\u0026quot;In some communities, cultural practices are powerful even more so than religious beliefs. That is why we should separate them, so our questions can be more accurate.\u0026quot; (P5)\u003c/em\u003e\u003c/p\u003e\n\u003cp\u003eInstead of perceiving this as a challenge, the experts recognised it as an opportunity to enhance the model\u0026rsquo;s precision and relevance. By disaggregating these constructs, vaccine outreach can be more effectively tailored in the future. Religious messages could be conveyed through trusted faith leaders, while cultural norms might be addressed by community elders or during traditional events. This level of targeted communication is essential in public health, as a one-size-fits-all approach often fails to address the needs of diverse populations.\u003c/p\u003e\n\u003cp\u003eOne panellist further underscored this point by noting the importance of acknowledging the distinct weight of these influences in shaping vaccine attitudes:\u003c/p\u003e\n\u003cp\u003e\u0026quot;\u003cem\u003eReligion is often the first reference point for many people, but culture and tradition carry their own authority that cannot be ignored\u003c/em\u003e.\u0026quot; (P7)\u003c/p\u003e\n\u003cp\u003eThis insight underscores the complex reality of Malaysian society, where individuals navigate intertwined systems of meaning when making health decisions. It reinforces the notion that a singular framework would oversimplify these variations, potentially misrepresenting respondents\u0026apos; true motivations. Furthermore, recognising these parallel yet distinct domains enables researchers to craft survey items that more accurately represent the decision-making processes of diverse demographic groups.\u003c/p\u003e\n\u003cp\u003eBy the conclusion of the discussion, it became evident that the panel not only endorsed the inclusion of these constructs but also regarded their differentiation as a vital refinement. Their insights reaffirm the conceptual trajectory of the proposed model and enhance its practical significance. By recognising that religion, culture, and tradition each hold distinct roles in influencing public attitudes, this research presents a more culturally informed and communicatively effective framework for fostering vaccine trust across diverse communities. Building on these reflections, the panel strongly recommended that religiosity, traditions, and culture be treated as distinct yet interrelated constructs, rather than collapsed into a single category. Such disaggregation not only provides greater conceptual clarity but also allows researchers and policymakers to identify which of these factors exerts the most decisive influence in different community settings, thereby enhancing both the theoretical robustness and the practical applicability of the model.\u003c/p\u003e\n\u003cp\u003e\u003cstrong\u003e3.2 Knowledge \u0026amp; Awareness\u003c/strong\u003e\u003c/p\u003e\n\u003cp\u003eIn discussing the behavioural and cognitive constructs included in the proposed model, the experts were quick to agree that \u003cstrong\u003eknowledge plays a pivotal role in shaping a person\u0026rsquo;s decision to receive the COVID-19 vaccine\u003c/strong\u003e\u003cstrong\u003e.\u0026nbsp;\u003c/strong\u003eIn their view, what the public truly knows, especially about complex immunological terms like Antibody-Dependent Enhancement (ADE) and cross-reactive immunity, often determines how confident they feel in accepting or rejecting vaccination. However, they also emphasised the importance of distinguishing this construct from awareness, which they described as a more superficial form of recognition. In Malaysia\u0026rsquo;s diverse information landscape, where people are exposed to health messages through various channels, this distinction becomes crucial not only theoretically but also practically, for both measurement and public health strategy (Md Norman \u0026amp; Mohamad Nasir, 2025; Perumal et al., 2024; Nen \u0026amp; Hamzah, 2023).\u003c/p\u003e\n\u003cp\u003eThe panel clarified that awareness pertains to exposure\u0026mdash;the capacity to recall having seen or heard something. Conversely, knowledge signifies a deeper level of understanding, including the ability to explain or apply a concept. One participant noted that survey design can obscure this distinction if not approached with care.\u003c/p\u003e\n\u003cp\u003e\u003cem\u003e\u0026ldquo;If we explain first, respondents might answer based on what they just read. That is not real knowledge.\u0026rdquo;\u003c/em\u003e (P4)\u003c/p\u003e\n\u003cp\u003eThis reflection drew nods from other participants, who believed that \u003cstrong\u003epre-survey definitions\u003c/strong\u003e, while meant to help, may unintentionally influence responses and inflate knowledge scores. Another expert suggested that \u003cstrong\u003emerging the two constructs\u003c/strong\u003e could compromise the validity of the findings:\u003c/p\u003e\n\u003cp\u003e\u003cem\u003e\u0026ldquo;I believe we should separate awareness and knowledge. They are two different constructs and require properly designed questions.\u0026rdquo;\u003c/em\u003e (P1)\u003c/p\u003e\n\u003cp\u003eThe concern extended beyond mere semantics. The experts expressed a firm belief that assessing both layers, first by determining whether respondents had heard of ADE or cross-reactive immunity (awareness), and then by asking them to explain or apply these concepts (knowledge), would yield a more accurate and comprehensive understanding of public awareness. One panellist elaborated further.\u003c/p\u003e\n\u003cp\u003e\u003cem\u003e\u0026ldquo;Respondents may answer based on new information they just read, not what they already knew. That could affect the results.\u0026rdquo;\u003c/em\u003e (P3)\u003c/p\u003e\n\u003cp\u003eAs the conversation deepened, the panel began offering suggestions on how to strengthen the model. They proposed that \u003cstrong\u003equestions be divided into two tiers, with awareness as the first tier\u003c/strong\u003e, followed by knowledge, so that researchers could identify exactly where the gaps lie.\u003c/p\u003e\n\u003cp\u003e\u003cem\u003e\u0026ldquo;I suggest using two levels, one for awareness, and another for deeper knowledge. That way, we can clearly see where the gaps are.\u0026rdquo;\u003c/em\u003e (P5)\u003c/p\u003e\n\u003cp\u003eAnother participant noted how this method could be beneficial when assessing technical terms:\u003c/p\u003e\n\u003cp\u003e\u003cem\u003e\u0026ldquo;If we are going to ask about ADE or cross-reactive immunity, we must make sure people understand the meaning first. Otherwise, they will just guess.\u0026rdquo;\u003c/em\u003e (P2)\u003c/p\u003e\n\u003cp\u003eBy the end of the session, the experts fully supported the decision to keep both constructs in the model, provided they are clearly distinguished in both theory and measurement. Their feedback directly strengthens the proposed model, which aims to assess not just what people are exposed to, but what they genuinely understand. This two-layered approach, which involves awareness followed by knowledge, provides a more transparent lens for public health communicators and researchers to design more targeted education campaigns that not only inform but also truly empower. Importantly, awareness and knowledge are crucial when addressing complex issues such as antibody-dependent enhancement (ADE) and cross-reactive immunity, as these concepts significantly influence how the public perceives vaccine safety and effectiveness.\u003c/p\u003e\n\u003cp\u003e\u003cstrong\u003e3.3 Applicability of the Model for Public Health Policy and Trust \u0026amp; Governance\u003c/strong\u003e\u003c/p\u003e\n\u003cp\u003eThe discussion revealed that the model\u0026rsquo;s novelty lies in its ability to integrate behavioural, cultural, and governance dimensions, making it both a theoretical and operational tool. As the discussion evolved toward practical applications, the expert panel smoothly transitioned from critique to collaboration. There was a strong and shared belief that the proposed conceptual model, depicted in Figure 1, offers significant potential beyond its academic merit. The experts collectively acknowledged that the model transcends a mere diagram or theoretical framework; it can be transformed into a strategic tool for guiding public health decisions, particularly in the realms of vaccine communication, addressing public hesitancy, and enhancing trust in governance structures, including transparency, ethical compliance, and institutional credibility.\u003c/p\u003e\n\u003cp\u003eWhat stood out in their responses was a belief that the model\u0026rsquo;s strength lies in its layered structure, which combines knowledge, sociocultural beliefs, risk perception, and behavioural support. In the words of one expert:\u003c/p\u003e\n\u003cp\u003e\u003cem\u003e\u0026quot;This model could help the Ministry of Health (KKM) identify communities that are hesitant about vaccines.\u0026quot;\u003c/em\u003e (P3)\u003c/p\u003e\n\u003cp\u003eThis perspective resonated deeply with other panellists, who felt that \u003cstrong\u003eMalaysia\u0026rsquo;s rich diversity requires more than a one-size-fits-all communication strategy\u003c/strong\u003e\u003cstrong\u003e.\u003c/strong\u003e They believed that the model could help \u003cstrong\u003emap patterns of concern\u003c/strong\u003e, allowing policymakers to pinpoint who needs what kind of messaging, whether it is scientific explanation, religious reassurance, or culturally relevant storytelling.\u003c/p\u003e\n\u003cp\u003eOne participant reflected on the practicality of the model\u0026rsquo;s framework:\u003c/p\u003e\n\u003cp\u003e\u003cem\u003e\u0026quot;If we know which communities have higher risk or lower understanding, we can develop more targeted interventions.\u0026quot;\u003c/em\u003e (P4)\u003c/p\u003e\n\u003cp\u003eAnother participant built on this by suggesting that the model\u0026rsquo;s utility goes beyond COVID-19, noting its \u003cstrong\u003eflexibility for long-term use\u003c/strong\u003e\u003cstrong\u003e:\u003c/strong\u003e\u003c/p\u003e\n\u003cp\u003e\u003cem\u003e\u0026quot;For long-term intervention, we could adapt this model for other vaccines too.\u0026quot;\u003c/em\u003e (P2)\u003c/p\u003e\n\u003cp\u003eThis initiated a broader conversation regarding its future adaptability. Panellists proposed that the same framework could be applied to campaigns for HPV, dengue, or even potential future pandemics, as long as the constructs are regularly updated to reflect evolving scientific and cultural landscapes. One participant suggested that the model could serve as a monitoring tool, revisited annually to evaluate public sentiment.\u003c/p\u003e\n\u003cp\u003e\u003cem\u003e\u0026quot;This model could work like a GPS; we use it to track where public thinking is headed and adjust our route when needed.\u0026quot;\u003c/em\u003e (P1)\u003c/p\u003e\n\u003cp\u003eThis analogy sparked further ideas about how the model could be operationalised on the ground. Another panellist emphasised the importance of \u003cstrong\u003etraining communicators and frontliners\u003c/strong\u003e using the framework to ensure the message delivery was just as effective as the message content:\u003c/p\u003e\n\u003cp\u003e\u003cem\u003e\u0026quot;If this model is to be used in the field, health workers must be trained to understand what each construct means.\u0026quot;\u003c/em\u003e (P3)\u003c/p\u003e\n\u003cp\u003ePanel 9 strongly affirmed that the successful implementation of the model depends on a firm commitment to transparency and accountability within the institutions involved.\u0026nbsp;\u003c/p\u003e\n\u003cp\u003e\u003cem\u003e\u0026quot;Any model will only work if the public feels that the government is honest and consistent in its communication.\u0026quot; (P9)\u003c/em\u003e\u003c/p\u003e\n\u003cp\u003eThis reflection highlights that the effectiveness of a model is not solely determined by its technical design; it also significantly depends on the implementation of trust-building measures at the policy level. Without credible and transparent institutions, even a well-structured framework may fail to gain public confidence, making it challenging to influence behaviour. Furthermore, it emphasises the strong interconnection between governance and health communication, underscoring that the acceptance of policies primarily relies on the public\u0026apos;s perception of fairness, consistency, and sincerity in government actions.\u003c/p\u003e\n\u003cp\u003eBy the end of the session, it became evident that the experts regarded the model not as a static entity, but as a dynamic, evolving tool. They valued its potential to connect academic research with the operational realities on the ground. Most importantly, they recognised that it honours the cultural, religious, and emotional dimensions often overlooked in public health planning, while also underscoring that trust in government and health institutions is a crucial factor for policy effectiveness. Their feedback underscores the model\u0026apos;s originality and significance, not only as a conceptual contribution but also as a potential framework for translating evidence into action precisely where it matters most. This reinforces the model\u0026apos;s applicability to public health policy and aligns with previous studies highlighting the necessity of integrating sociocultural, religious, and behavioural aspects into vaccine communication strategies (Tiwana \u0026amp; Smith, 2024; Dhaliwal et al., 2024; Danmaisoro \u0026amp; Eledi, 2024). Similar to the models used in COVID-19 vaccine campaigns and HPV vaccination programs, this framework illustrates how academic insights can be applied to inform national interventions, thereby enhancing their relevance for both current and future vaccination challenges.\u0026nbsp;\u003c/p\u003e\n\u003cp\u003e\u003cstrong\u003e3.4 Future Adaptability, Digital Health Literacy, and Strategic Use\u003c/strong\u003e\u003c/p\u003e\n\u003cp\u003eAs the discussion transitioned to its final theme, the focus naturally shifted toward the future. The expert panel expressed optimism regarding the proposed model\u0026apos;s potential to evolve, adapt, and serve beyond the immediate challenges posed by COVID-19. Initially conceived as a conceptual tool to analyse vaccine perceptions during the pandemic, they believed that this model was well-positioned to emerge as a versatile framework for long-term public health planning. The panel highlighted the model\u0026apos;s layered structure, which integrates sociocultural, behavioural, and immunological constructs, describing it as \u0026quot;modular\u0026quot; and \u0026quot;future-proof.\u0026quot; This approach provides a blueprint that can be effectively repurposed for various vaccination campaigns, targeting seasonal influenza, HPV, or emerging health threats yet to be identified.\u003c/p\u003e\n\u003cp\u003eOne panellist expressed appreciation for the model\u0026rsquo;s adaptability but encouraged theoretical reinforcement to enhance its credibility and utility:\u003c/p\u003e\n\u003cp\u003e\u0026nbsp;\u003cbr\u003e\u003cem\u003e\u0026quot;We can use this model for HPV or influenza vaccines too, but it should be strengthened with theories like the Health Belief Model.\u0026quot; (P4)\u003c/em\u003e\u003c/p\u003e\n\u003cp\u003eThe concept struck a chord with others, who recognised the significant potential in aligning the model with established behavioural frameworks, such as the Health Belief Model (HBM) and other models related to vaccine acceptance. They argued that these frameworks could offer a more robust foundation for understanding public decision-making by incorporating factors such as perceived risks, trust in the system, and the accessibility of information.\u003c/p\u003e\n\u003cp\u003e\u003cbr\u003e\u003cem\u003e\u0026quot;To understand why people accept or reject vaccines, we also need to consider their trust and how they interact with technology.\u0026quot; (P6)\u003c/em\u003e\u003c/p\u003e\n\u003cp\u003eAnother participant proposed integrating digital health literacy and communication channels into the model to reflect current realities, where health information spreads rapidly both accurately and otherwise online:\u003c/p\u003e\n\u003cp\u003e\u003cbr\u003e\u003cem\u003e\u0026quot;I suggest including digital literacy as part of the model too.\u0026quot; (P8)\u003c/em\u003e\u003c/p\u003e\n\u003cp\u003eThis prompted a deeper consideration of how practitioners could utilise the model in practical settings. The experts envisioned its concepts not only guiding surveys and academic publications but also being integrated into training programs for healthcare workers, risk communication strategies, and national vaccine education initiatives.\u003c/p\u003e\n\u003cp\u003e\u003cbr\u003e\u003cem\u003e\u0026quot;If we want to apply this model practically, we must also think about who will deliver the message, and how.\u0026quot; (P1)\u003c/em\u003e\u003c/p\u003e\n\u003cp\u003eNotably, the panel also suggested building feedback loops into the model\u0026rsquo;s design, allowing it to evolve as more data becomes available or as societal norms shift:\u003c/p\u003e\n\u003cp\u003e\u003cbr\u003e\u003cem\u003e\u0026quot;This model should be updated in line with social changes. It should not be static; it should stay dynamic and relevant.\u0026quot; (P2)\u003c/em\u003e\u003c/p\u003e\n\u003cp\u003eBy the end of the conversation, it was evident that the panel viewed the proposed model not as a final product, but as a living framework capable of being refined, expanded, and applied across various public health contexts. Its core value, they agreed, lies in its cultural sensitivity, theoretical flexibility, and practical usability. In their view, the model\u0026rsquo;s greatest strength is its potential to serve as a bridge connecting what experts know with how communities live, believe, and decide. This underscores the model\u0026rsquo;s future adaptability and strategic use, echoing previous research which highlights the importance of flexible, theory-informed frameworks in addressing vaccine hesitancy and guiding long-term health strategies (Betsch et al., 2018; Larson, 2018b). In particular, embedding digital health literacy ensures resilience against misinformation, while the inclusion of trust and governance highlights the critical role of institutional legitimacy in sustaining vaccine confidence.Similar to approaches used in studies on influenza, HPV, and dengue vaccination campaigns, the integration of behavioural theory, sociocultural insights, and digital literacy has been shown to enhance both the reach and effectiveness of public health interventions (Hornsey et al., 2018; Nagyova, 2024; Mancone et al., 2024). Thus, the proposed model aligns with and extends existing scholarship, positioning it as a valuable tool for shaping responsive and inclusive vaccine policies in the years to come.\u003c/p\u003e"},{"header":"4. Discussion","content":"\u003cp\u003eThis study provides nuanced insights into the interplay of sociocultural, behavioural, and immunological factors that influence vaccine perceptions in a multi-ethnic and multi-faith society. By utilising a conceptual framework that integrates elements from the Health Belief Model (HBM) and the Arham Model, while also introducing scientifically specific constructs such as awareness of Antibody-Dependent Enhancement (ADE) and understanding of cross-reactive immunity, the research fosters a multidimensional perspective on vaccine acceptance. The findings not only affirm but also extend prior research by revealing that vaccine hesitancy in Malaysia is influenced not just by individual risk perceptions or access to healthcare, but also by deeply rooted social norms, religious beliefs, and cognitive interpretations of scientific phenomena (Balakrishnan et al., 2024; Marzo et al., 2023; Lee et al., 2023).\u003c/p\u003e\n\u003cp\u003eA significant contribution of this study is its clear disaggregation of religious, cultural, and traditional constructs, a methodological choice that has been supported by robust feedback from expert participants. Previous literature frequently treated these elements as interchangeable or overlapping, which risks oversimplifying their distinct influences on public behaviour (Ngcobo \u0026amp; Zhandire, 2025; Kitayama \u0026amp; Salvador, 2024). Our findings, which align with those of Begum et al. (2024), reveal that religious frameworks often dictate vaccine permissibility, particularly in relation to halal status and the concept of divine protection. Conversely, cultural norms shape intergenerational dialogues surrounding medical interventions, while traditional practices may either reinforce or challenge biomedical recommendations. For example, cultural events or family rituals might serve as venues for either support or resistance to vaccination, depending on community-specific interpretations. This aligns with the perspectives of Ali Sheikhi et al. (2025), who contend that targeted communication through religious leaders and cultural gatekeepers significantly enhances vaccine uptake. By structurally separating these elements, the proposed model facilitates a more precise identification of drivers of hesitancy and enables communication strategies that are not only context-sensitive but also tailored to specific constructs.\u003c/p\u003e\n\u003cp\u003eFurthermore, the study highlights the importance of distinguishing between awareness and knowledge, a distinction that has become increasingly crucial in discussions surrounding vaccine literacy. Awareness involves recognition and recall, while knowledge encompasses factual understanding and the capacity to apply information appropriately in context (Silva \u0026amp; Siscoe, 2025; Wong et al., 2022; Fernández-Fernández, 2021; Silva, 2021). Numerous studies have indicated that during the COVID-19 pandemic, a high level of awareness without a corresponding depth of knowledge rendered populations more susceptible to misinformation, particularly concerning complex immunological topics such as Antibody-Dependent Enhancement (ADE) and cross-reactive immunity (Marzo et al., 2022). In this study, experts expressed concern about the potential inflation of knowledge scores when respondents receive explanations during the survey (Abdelrahman et al., 2022). This apprehension is consistent with earlier critiques by Park and Kim (2021) regarding the construct validity of health literacy tools.\u003c/p\u003e\n\u003cp\u003eThe model’s two-tiered measurement design, separating recognition (awareness) from understanding (knowledge), facilitates more accurate detection of cognitive gaps. This granularity is essential for designing layered health communication interventions, whereby surface-level exposure can be followed up with more in-depth educational content, tailored to specific audience profiles. Such an approach resonates with the WHO’s (2022) call for audience segmentation in vaccine messaging, ensuring that the content not only informs but also resonates cognitively and emotionally with the public.\u003c/p\u003e\n\u003cp\u003eBeyond theoretical alignment, the model was endorsed by experts for its policy utility, particularly for its capacity to guide intervention design in real-world contexts. The structure was seen as robust yet adaptable, capable of identifying patterns of vaccine hesitancy at community and national levels. These findings parallel existing literature suggesting that models incorporating sociocultural and behavioural constructs can enhance predictive accuracy in public health strategies (Lee et al., 2023). In the Malaysian context, this is particularly relevant given the prior success of culturally framed HPV and influenza vaccine campaigns (Wong et al., 2021). The expert panel specifically noted that the proposed model could support targeted risk communication, resource allocation, and prioritisation of high-hesitancy zones, consistent with WHO's strategic framework for COVID-19 vaccine deployment (WHO, 2022).\u003c/p\u003e\n\u003cp\u003eThe model's adaptability across various disease contexts was further highlighted by participants, who recognised its potential utility in upcoming vaccination initiatives that span from emerging infectious diseases to routine immunisation programs. This observation aligns with the broader trend in public health frameworks towards modular and scalable models that can be adjusted to meet evolving epidemiological demands (Limbu et al., 2022; Freeman et al., 2022). A key recommendation from the expert group was to enhance the theoretical robustness of the model by incorporating established behavioural models, in addition to the Health Belief Model and the Arham Model. This integration would help account for the increasingly significant roles of digital health information systems, online trust, and social media influence. Empirical evidence supports this suggestion, indicating that digital trust and eHealth literacy are critical predictors of vaccine confidence among tech-savvy populations (Ashfield et al., 2024; Bíró et al., 2023).\u003c/p\u003e\n\u003cp\u003eAdditionally, the call to embed digital literacy as a formal construct within the model addresses an important emerging dimension of vaccine communication. As shown in a recent cross-national study by Wells et al. (2025), misinformation thrives in the absence of digital critical thinking skills, particularly when scientific terminology (e.g., \"antibody-dependent enhancement\") is misunderstood or misused. Integrating such components into the model ensures its relevance within the digital communication ecosystem while allowing for longitudinal adaptability as new platforms and health technologies emerge.\u003c/p\u003e\n\u003cp\u003eIn conclusion, the four themes identified: religious, cultural, and traditional constructs; the distinction between awareness and knowledge; policy applicability with an emphasis on trust and governance; and future adaptability, particularly concerning Digital Health Literacy, form the foundation of the refined model presented in Figure 2. This model effectively integrates scientific concepts, such as antibody-dependent enhancement (ADE) and cross-reactive immunity, with sociocultural sensitivities to provide a comprehensive understanding of vaccine acceptance. By evolving from the conceptual framework in Figure 1 to the empirically informed model in Figure 2, the study demonstrates how theoretical insights can be transformed into a culturally grounded framework for practical applications. Importantly, the refined model embodies a “better safe than sorry” approach to public acceptance of vaccination, ensuring that immunisation strategies are not only scientifically robust but also socially resonant across diverse ethnic and faith communities.\u003c/p\u003e"},{"header":"5. Conclusion","content":"\u003cp\u003eThis study offers valuable insights into how expert perspectives shape the public's understanding of immunological risks, particularly regarding Antibody-Dependent Enhancement (ADE) and cross-reactive immunity in the context of COVID-19 vaccination in Malaysia. Through thematic analysis of focus group discussions, the findings highlight the necessity of distinguishing between various constructs such as religion, culture, and tradition, as well as between awareness and knowledge, each of which plays a unique role in shaping vaccine acceptance. The experts endorsed the proposed integrated model, which combines the Health Belief Model (HBM), the Arham Model, and novel scientific constructs, as a flexible and contextually relevant tool for guiding vaccine communication and public health policy. Their recommendations to incorporate digital literacy and behavioural theory further enhance the model’s adaptability across diverse populations and future immunisation initiatives. Ultimately, this research achieves its goal by presenting a comprehensive and culturally grounded model of public acceptance that can inform science communication, address vaccine hesitancy, and support evidence-based immunisation strategies in Malaysia and beyond.\u003c/p\u003e\n\u003cp\u003e\u003cbr\u003e\u003c/p\u003e"},{"header":"Declarations","content":"\u003cp\u003e\u003cstrong\u003eAcknowledgement\u003c/strong\u003e\u003c/p\u003e\n\u003cp\u003eThe research was funded by the Ministry of Higher Education (MOHE), grant number CITRA-2024-003, and Universiti Kebangsaan Malaysia for its support of this research.\u003c/p\u003e\n\u003cp\u003e\u003cstrong\u003eFunding\u003c/strong\u003e\u003c/p\u003e\n\u003cp\u003eThis study was supported by the CITRA-2024-003 grant from the Ministry ofHigher Education (MOHE), Malaysia. The funder provided funding to conduct surveys related to this research. Still, it did not have a significant role in the study design, data collection and analysis, the decision to publish, or the preparation of the manuscript.\u003c/p\u003e\n\u003cp\u003e\u003cstrong\u003eContributions\u003c/strong\u003e\u003c/p\u003e\n\u003cp\u003eAhmad Firdhaus Arham, Nurhafiza Zainal, Mohd Istajib Mokhtar, and Chin Kim Ling conceptualised the study and supervised the project. Maizatul Shazwani Mohd Rus Aznan, Yusnaini Md Yusoff, Nur Asmadayana Hasim, Noor Sharizad Rusly, and Ahmad Firdhaus Arham prepared the original draft, developed the methodology, validated the findings, and conducted the formal analysis. Maizatul Shazwani Mohd Rus Aznan, Nur Asmadayana Hasim, and Ahmad Firdhaus Arham reviewed and edited the manuscript. Ahmad Firdhaus Arham acquired funding and conducted the final review of the study.\u003c/p\u003e\n\u003cp\u003e\u003cstrong\u003eCorresponding authors\u003c/strong\u003e\u003c/p\u003e\n\u003cp\u003eCorrespondence to\u0026nbsp;Ahmad Firdhaus Arham and Nur Asmadayana Hasim.\u003c/p\u003e\n\n\u003cp\u003e\u003cstrong\u003eCompeting interests\u003c/strong\u003e\u003c/p\u003e\n\u003cp\u003eThe authors declare no competing interests.\u003c/p\u003e\n\u003cp\u003e\u003cstrong\u003eEthical Approval\u003c/strong\u003e\u003c/p\u003e\n\u003cp\u003eEthical approval for this study was obtained from the University of Malaya Research Ethics Committee (UMREC) under Reference Number UM.TNC2/UMREC_4334, approved on 20 March 2025 (valid until March 2028).\u003c/p\u003e\n\u003cp\u003e\u003cstrong\u003eInformed Consent\u003c/strong\u003e\u003c/p\u003e\n\u003cp\u003eWritten informed consent was obtained from all participants. Participant selection began in April 2025, invitations were sent on 13 June 2025, and the FGD was conducted on 25 June 2025 at the Bangi Golf Resort, Selangor, Malaysia.\u003c/p\u003e"},{"header":"References","content":"\u003col\u003e\u003cli\u003e\u003cspan\u003eAbdelrahman G, Wang Q, Nunes B (2022) Knowledge Tracing: A Survey. ACM-CSUR 55:1\u0026ndash;37. \u003cspan class=\"ExternalRef\"\u003e\u003cspan class=\"RefSource\"\u003ehttps://doi.org/10.1145/3569576\u003c/span\u003e\u003cspan address=\"10.1145/3569576\" targettype=\"DOI\" class=\"RefTarget\"\u003e\u003c/span\u003e\u003c/span\u003e\u003c/span\u003e\u003c/li\u003e\u003cli\u003e\u003cspan\u003eAhmad MK, Othman MBMH, Jalil NHM, Ismail S (2021) Model komunikasi kesihatan kepekaan budaya: Suatu penerokaan dalam kalangan golongan muda Muslim di Malaysia. 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Front Public Health 12:1457266. \u003cspan class=\"ExternalRef\"\u003e\u003cspan class=\"RefSource\"\u003ehttps://doi.org/10.3389/fpubh.2024.1457266\u003c/span\u003e\u003cspan address=\"10.3389/fpubh.2024.1457266\" targettype=\"DOI\" class=\"RefTarget\"\u003e\u003c/span\u003e\u003c/span\u003e\u003c/span\u003e\u003c/li\u003e\u003c/ol\u003e"}],"fulltextSource":"","fullText":"","funders":[],"hasAdminPriorityOnWorkflow":false,"hasManuscriptDocX":true,"hasOptedInToPreprint":true,"hasPassedJournalQc":"","hasAnyPriority":false,"hideJournal":true,"highlight":"","institution":"","isAcceptedByJournal":false,"isAuthorSuppliedPdf":false,"isDeskRejected":"","isHiddenFromSearch":false,"isInQc":false,"isInWorkflow":false,"isPdf":false,"isPdfUpToDate":true,"isWithdrawnOrRetracted":false,"journal":{"display":true,"email":"[email protected]","identity":"researchsquare","isNatureJournal":false,"hasQc":true,"allowDirectSubmit":true,"externalIdentity":"","sideBox":"","snPcode":"","submissionUrl":"/submission","title":"Research Square","twitterHandle":"researchsquare","acdcEnabled":true,"dfaEnabled":false,"editorialSystem":"","reportingPortfolio":"","inReviewEnabled":false,"inReviewRevisionsEnabled":true},"keywords":"COVID-19 vaccine, antibody-dependent enhancement (ADE), cross-reactive immunity, Vaccine acceptance, Science communication","lastPublishedDoi":"10.21203/rs.3.rs-7530895/v1","lastPublishedDoiUrl":"https://doi.org/10.21203/rs.3.rs-7530895/v1","license":{"name":"CC BY 4.0","url":"https://creativecommons.org/licenses/by/4.0/"},"manuscriptAbstract":"\u003cp\u003eThe COVID-19 pandemic has underscored the crucial importance of vaccination; however, public acceptance in Malaysia is influenced not only by access and trust but also by cultural, religious, and scientific considerations. In the Klang Valley, a highly urbanised and demographically diverse region, vaccine uptake has been relatively high. Nonetheless, scepticism remains, particularly regarding complex immunological issues such as antibody-dependent enhancement (ADE) and cross-reactive immunity. This study seeks to inform the development of a comprehensive public acceptance model for immunisation by integrating expert insights into these scientific concerns, along with socio-cultural and religious contexts. A focus group discussion (FGD) was conducted involving nine experts in public health, immunology, and vaccine policy. The transcribed data were analyzed using Reflexive Thematic Analysis, leading to the emergence of four key themes: (1) Disentangling religious, cultural, and traditional constructs; (2) Distinguishing awareness from knowledge of scientific risks; (3) Practical applicability for public health communication and policy; and (4) Model adaptability, including potential applications for other vaccines such as HPV and dengue. This study uniquely combines the Arham Model with the Health Belief Model (HBM) to create a culturally grounded framework that acknowledges both the behavioural and immunological dimensions of vaccine acceptance. By emphasising the significance of science communication, sociocultural sensitivity, and theoretical integration, this work contributes a novel, adaptable model for guiding immunisation strategies in Malaysia, offering insights that are relevant to broader global contexts.\u003c/p\u003e","manuscriptTitle":"Integrating Scientific Concerns on Antibody-Dependent Enhancement and Cross-Reactive Immunity with Cultural Contexts: A “Better Safe than Sorry” Model for Public Acceptance of Vaccination","msid":"","msnumber":"","nonDraftVersions":[{"code":1,"date":"2025-10-17 13:03:05","doi":"10.21203/rs.3.rs-7530895/v1","editorialEvents":[{"type":"communityComments","content":0}],"status":"published","journal":{"display":true,"email":"[email protected]","identity":"researchsquare","isNatureJournal":false,"hasQc":true,"allowDirectSubmit":true,"externalIdentity":"","sideBox":"","snPcode":"","submissionUrl":"/submission","title":"Research Square","twitterHandle":"researchsquare","acdcEnabled":true,"dfaEnabled":false,"editorialSystem":"","reportingPortfolio":"","inReviewEnabled":false,"inReviewRevisionsEnabled":true}}],"origin":"","ownerIdentity":"1449dfda-1eac-4fa1-8e86-b3827c020ad1","owner":[],"postedDate":"October 17th, 2025","published":true,"recentEditorialEvents":[],"rejectedJournal":[],"revision":"","amendment":"","status":"posted","subjectAreas":[{"id":56432018,"name":"Humanities/Cultural and media studies"},{"id":56432019,"name":"Social science/Cultural and media studies"},{"id":56432020,"name":"Humanities/Health humanities"},{"id":56432021,"name":"Biological sciences/Immunology"},{"id":56432022,"name":"Humanities/Medical humanities"},{"id":56432023,"name":"Social science/Social policy"}],"tags":[],"updatedAt":"2026-02-10T20:24:06+00:00","versionOfRecord":[],"versionCreatedAt":"2025-10-17 13:03:05","video":"","vorDoi":"","vorDoiUrl":"","workflowStages":[]},"version":"v1","identity":"rs-7530895","journalConfig":"researchsquare"},"__N_SSP":true},"page":"/article/[identity]/[[...version]]","query":{"redirect":"/article/rs-7530895","identity":"rs-7530895","version":["v1"]},"buildId":"8U1c8b4HqxoKbykW_rLl7","isFallback":false,"isExperimentalCompile":false,"dynamicIds":[84888],"gssp":true,"scriptLoader":[]}