Immunogenicity and Safety of Polio Vaccines in Infants: A Systematic Review of Randomized Clinical Trials

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Terekhov, Artem A. Svotin, Maria D. Korochkina, Anastasiya A. Khodyachikh, and 6 more This is a preprint; it has not been peer reviewed by a journal. https://doi.org/ 10.21203/rs.3.rs-6913898/v1 This work is licensed under a CC BY 4.0 License Status: Published Journal Publication published 29 Oct, 2025 Read the published version in Virology Journal → Version 1 posted 13 You are reading this latest preprint version Abstract Poliomyelitis, preventable only through vaccination, remains a global health concern, with wild poliovirus transmission and the emergence of vaccine-derived polioviruses. The risk of further deterioration of the situation jeopardizes efforts to eradicate polio, which has been a long-term goal for the whole world. In this systematic review an analysis of randomized clinical trials was carried out to comprehensively assess the immunogenicity and safety of various polio immunization methods in infants. Geometric mean neutralizing antibody titers (GMT) data collected after 28–31 days after immunization were used to calculate the geometric mean titers ratio (GMR), the analysis of which showed that both inactivated polio vaccine (IPV) and Sabin strain-based inactivated polio vaccine (sIPV) as primary vaccination induce high antibody rates, with fractional IPV showing similar results. Novel oral polio vaccine type 2 and trivalent oral polio vaccine (tOPV) also demonstrated immunogenicity in establishing immunity comparable to inactivated vaccine. High antibody levels were also induced by combined vaccine schedules, with sIPV-sIPV-bOPV and IPV combinations with diphtheria-tetanus-acellular and Haemophilus influenzae type b or pentavalent rotavirus vaccine establishing particularly high antibody levels. Analysis of adverse events presented all vaccines to be well-tolerated and safe, with a tendency of combination vaccines having higher frequency of local reactions and fever. While the studies presented a various landscape with some existing areas of concern, this review provides structured evidence supporting the safety and immunogenicity of existing polio vaccines, as well as highlighting the interchangeability of different vaccination approaches in infants. Future research should aim to provide detailed reporting of adverse events in order to facilitate more comprehensive assessment of vaccine efficacy. Poliomyelitis Vaccines Immunization Immunogenicity Infants Systematic Review Randomized Clinical Trials Figures Figure 1 Figure 2 Figure 3 Introduction Poliomyelitis is a highly contagious disease that can be contracted by an unvaccinated person of any age but disease more often occurs in children under 5 years of age. The causative agent of this disease is poliovirus, a small, non-enveloped virus containing a single-stranded positive-sense RNA genome, about 7,500 nucleotides long, enclosed in a protein capsid. The capsid is made up of 60 protomers composed of four viral proteins (VP 1–4) arranged in icosahedral symmetry, with VP 1–3 creating antigenic sites for receptor and antibodies to bind. Based on the slight differences in the capsid structure, three types of polioviruses (type 1, 2 and 3) are distinguished 1 , 2 , 3 , 4 . There is no cure for polio, and the nerve damage and paralysis that it causes can be permanent or even fatal 5 . The only way of preventing the disease is through vaccination, which has proven to be effective against all 3 types of poliovirus. The main two forms of polio vaccine are oral polio vaccine (OPV) and inactivated polio vaccine (IPV) 6 , 7 . Both OPV and IPV have been widely applied since the 1950-60s and continue to be a crucial part of the Global Polio Eradication Initiative (GPEI)– since its launch in 1988 polio incidence has globally decreased by over 99%, leaving only the wild polioviruses type 1 still endemic in Pakistan and Afghanistan 5 , 8 , 9 . It is important to mention that, despite OPV inducing good intestinal immunity and being generally safe, the live attenuated polioviruses it contains can cause vaccine-associated paralytic poliomyelitis (VAPP) and mutate into circulating vaccine-derived polioviruses (cVDPV) able to cause polio cases and outbreaks 10 , 11 , 12 . Polio vaccine virus type 2 is mostly associated with VDPV2 and is responsible for most outbreaks. For this reason, global switch from trivalent OPV types 1, 2 and 3 to bivalent OPV types 1 and 3 was performed in 2016. This process included a transition to vaccination schedules that include IPV to maintain immunity to polioviruses type 2. Moreover, IPV it contains an inactivated virus and carries no risk of VAPP or VDPV 13 , 14 , 15 , 16 , 17 . Also, due to the increasing cost of GPEI, the question of its necessity arises, given the low number of polio cases and the nearly global routine immunization. Nevertheless, continuing the program is critical, and not only to ensure vaccination coverage, but also because it is a cost-effective decision with substantial long-term benefits that far outweigh the expenses. The cost of health care saved by preventing polio and related cases of paralysis is more than two to three times higher, than the cost of polio eradication in the long term. Over the years 1970–2050, polio vaccination will prevent about 42 million polio cases, and thus prevent about 855,000 deaths and more than 4 million paralysis cases 18 . In terms of disability-adjusted life years (DALYs), vaccination and polio eradication will save about 39.5 million years by the year 2050 18,19 . In recent years, low immunization coverage hinders the GPEI progress. Between 2021 and 2024 there were 2,406 paralysis cases recorded in regions such as parts of Africa, Yemen, and Indonesia, attributed to newly formed cVDPVs of all three types 20 . Moreover, in Afghanistan and Pakistan endemic transmission of wild poliovirus type 1 (WPV1) continues with increasing number of polio cases: in 2024 the total 99 cases were recorded in the area 10 , 21 . Moreover, this decline in vaccination has been intensified by numerous cases of misinformation and anti-vaccine activism that have emerged in the last couple of years. The most common misinformation pieces claimed that vaccines were unsafe and that they could cause other diseases. Battling such accusations by providing grounded proof is necessary, and is now more urgent than ever, as the GPEI sets 2026 as the year for complete polio eradication. The possibility of virus breakouts and further spread of misinformation on a wider scale is putting at risk the GPEI goal, hence it is extremely important to maintain high vaccination rates and to raise awareness of the importance of vaccination. Which is why the aim of this review is to provide a comprehensive summary of data regarding various immunization methods to demonstrate the immunogenicity and safety of existing polio vaccines. Materials and Methods Study design The design of this systematic review was conducted by the Preferred Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA) guidelines 22 . A protocol for this study has been registered on PROSPERO 23 under ID CRD42024574830 in August 2024 . Data sources A systematic search of papers was conducted using the following databases: PubMed/MEDLINE, Google Scholar, and eLibrary. Search strategy The search strategy in English combined the following terms: (poliomyelitis OR (infantile AND paralysis) OR “essential paralysis” OR “Heine-Medin disease” OR tephromyelitis OR polio) AND (immunogen* OR efficacy OR seroconversion) AND (vaccin* OR poliovaccine). In Russian the equal terms were used. Inclusion and exclusion criteria The inclusion and exclusion criteria were based on the PICOS principles 24 . They are summarized in Table 1 . Table 1 Inclusion and exclusion criteria. Criteria Inclusion Exclusion Population Infants (age from birth to 1 year) Males or females Healthy Any illness or medical condition Intervention Immunization by any polio vaccine Absence of immunization by any polio vaccine Control The presence of control group in analyzed publications is not necessary Outcome measure(s) Geometric mean neutralizing antibody titers (GMT) before immunization and at the day 21–31 after immunization Data separated depending on the polio serotype No GMT data before immunization No GMT data at the day 21–31 after immunization No serotype details for GMT data Study design Randomized clinical trials Study of any other design Only papers that provided the full text in English or Russian were included in the systematic review. Data collection All papers obtained from the databases were recorded in cloudified table. Duplicates were removed prior to screening. Two researchers (A.A.Kh. and M.A.V.) independently evaluated the article set according to including and excluding criteria, based on the titles and abstracts. In case of disagreement, the third researcher (Yu.Yu.I.) served as a referee. Then full texts of selected studies were assessed for eligibility. Data extraction Two reviewers (A.A.Kh. and M.A.V.) independently performed the data extraction. The following data were in focus: number of immunized patients, country of study; dose, timing, formulation, administration, combination, and valency of vaccine; antibody titer; side effects (number of cases), poliomyelitis cases (number of cases); bibliographical details. Data analysis Three researchers (R.P.T., A.A.S., and A.A.Kh.) performed the formal analysis of extracted data. To standardize the immunogenicity value of polio vaccines in selected studies the geometric mean titers ratio (GMR) was calculated, using the following formula: $$\:GMR=\:\frac{{GMT}_{n}}{{GMT}_{0}}$$ 1 , where GMT 0 is the GMT value before the immunization and GMT n is the GMT value at the day 21–31 after the immunization. The obtained GMR values, number side effect cases, and number of were combined based on the types of vaccines and patients’ characteristics. To evaluate the significance of differences between the groups in the analyzed parameters, the mean values and the confidence intervals were calculated ( p = 0.05). Risk of Bias assessment The included studies were independently assessed by the two researchers (M.D.K. and A.N.P.), using the version 2 of the Risk of Bias (RoB 2) tool 25 . The quality of evidence for the primary outcomes was evaluated via following bias domains: randomization process, deviations of intended interventions, missing outcome data, measurement of the outcome, and selection of the reported results. In case of discrepancies, they were resolved by a tiebreaker reviewer (L.I.K.). To visualize the results of RoB assessment, the ROBVIS tool was applied 26 . To evaluate the publication biases, the funnel plots were built in case of enough volume of data ( n ≥ 10). Results and Discussion General outlook on the scientific landscape Since 1984 the number of articles on polio vaccines has visibly increased. Over the past 10 years has reached about 60 articles on average per year (Fig. 1a). These data deposited in PubMed were used to build a bibliometric network based on keywords co-occurring with the terms “poliovirus” and “vaccine” in articles (Fig. 1b). The terms “humans”, “infant”, “male”, “female”, “poliovirus vaccines, inactivate”, “poliovirus vaccines, oral”, and “antibodies, viral” are the most frequently used, which is indicated by their bubble size. We also looked at the general publication trends of the twentieth century, and it was the middle of the 1980s when the number of studies on polio vaccines has begun to increase. The overall scientific background at the time did not experience any sudden changes while continuously growing since the late 1940s 27 . Therefore, such activity is most likely correlates with the global effort to eradicate polio that had begun in 1985 with the start of the PolioPlus initiative and was followed by the launch of the Global Polio Eradication Initiative (GPEI) in 1988. All national immunizations and polio monitoring campaigns were inevitably accompanied by a large volume of publications on these programs and their results. Clearly, the 1980s has become a turning point in the fight against polio, raising the global interest in collaborative polio eradication efforts that continue to be ongoing today 28 . It is also noteworthy, that there has been a shift in interest towards the immunogenicity of the polio vaccine in the recent years (Fig. 1c) that confirms the significance of the systematic review. In order to fully estimate the relevance of the review, a primary evaluation of the PROSPERO search results on the immunogenicity of polio vaccines was performed and showed that our analysis is not only relevant due to the lack of similar articles on polio vaccine, but also unique in the variety of different vaccines that were compared and assessed. Process of collection and selection of the studies A total of 1,845 articles were identified through the search strategies of Pubmed/MEDLINE, eLibrary and GoogleScholar. Before the screening, 102 duplicates were removed. After the first screening 1,600 articles did not meet the inclusion criteria based on their titles and abstracts, and therefore were excluded. After the second screening an additional of 48 articles were removed. During the final screening 75 records were excluded due to the following reasons: the absence of blood samples collection on days 21–31 after the last vaccination ( n = 37), patients are older than 1 year of age ( n = 3), use of median titers ( n = 19), no data on GMT ( n = 6), lack of initial data on antibody titers ( n = 6), other reasons ( n = 4). The total of 23 studies were included in this systematic review. The collection and selection process are illustrated in the PRISMA flow diagram (Fig. 2 ). 3.3 Qualitative synthesis A total of 15,052 participants were analyzed in the 23 included studies. 1,065 infants were assigned to the groups administered only IPV (Salk vaccine) 32 , 33 , 34 , 35 , 36 , another 969 infants to the groups which received IPV-Al (aluminium hydroxide-adjuvanted IPV) 32 , 37 as part of their immunization. A number of studies included administration of sIPV (IPV from Sabin strains) to a total of 3,406 infants 33 , 36 , 38 , 39 , 40 , . The efficacy of OPV (nOPV2, bOPV, tOPV) against polio strains was assessed in 3,738 participants 41 42 34 35 43 . One of the studies evaluated the effectiveness of a combined IPV and OPV (bOPV or tOPV) vaccination with 563 recipients 35 , and another trial was conducted with 374 recipients and the combination of sIPV and bOPV 38 . The majority of participants in the amount of 4,345 were administered some kind of combination of IPV 37 , 44 , 45 , 46 47 48 49 50 51 52 53 with DTaP/DTwP (diphtheria-tetanus-acellular/ whole-cell pertussis vaccine), Hib ( Haemophilus influenzae type b), PRP ∼ T (polyribose ribitol phosphate conjugated to tetanus protein), HBV (hepatitis B vaccine) or RV5 (pentavalent rotavirus vaccine) 54 ; combined vaccines with sIPV were administered to 592 participants 40 , 44 . In a single study 219 participants were administered a combination of DTwP-HB-Hib and bOPV with IPV 46 . The intervention method was either injection (intramuscular (IM), intradermal (ID), sequential (SC)) or oral administration ( per os ). In all of the studies a full dose of OPV was administered, IPV doses varied from a full to a reduced dose (1/ n , n = 3, 5, and 10) with one of the trials assessing the efficacy of a low, medium, and high dose. The findings from the 23 articles are summarized in Supplementary Table 1. For the same vaccines administered in more than 1 study the mean GMR was calculated (95% CI) and presented in Table 2 . Due to lack of clarification on the exact vaccines administered in studies with IPV or sIPV when trial subjects were allowed to be vaccinated with “other vaccines” according to the routine immunization schedule, these groups were not included in the mean GMR table. Table 2 Statistical processing of data from several articles. Type of polio vaccine Sample size Dosage form Average GMR, IU Serotype I Serotype II Serotype III IPV 1,065 INJ 1.0 83.08 ± 86.90 33.60 ± 18.78 166.30 ± 109.12 sIPV 3,406 INJ 1.0 234.35 ± 175.25 44.04 ± 12.58 163.13 ± 76.94 tOPV 374 Oral 1.0 257.55 ± 203.15 50.75 ± 28.13 88.05 ± 13.03 DTaP-IPV/Hib 651 INJ 1.0 129.27 ± 61.72 83.84 ± 17.42 247.87 ± 49.98 DTPa-HBV-IPV/ Hib 510 INJ 1.0 36.45 ± 39.10 42.50 ± 32.54 152.10 ± 71.73 *data are presented as average GMR ± half-width of the confidence interval ( p < 0.05) Risk of Bias Possible forms of bias were assessed according to the RoB 2 tool. Overall, 2 of the 23 studies showed a high risk of bias and 8 others raised some concerns. A “traffic light” summary of the “low”, “high”, or “some concerns” risk of bias assessment of the included studies via 5 domains is presented in Fig. 3 a. The weighted bar plot (Fig. 3 b) provides a graphical representation of the distribution of risk-of-bias judgments within each bias domain. Since the judgments are weighted, the segments represent the proportional distribution of studies categorized as “low,” “some concerns,” and “high.” Consequently, the overall risk-of-bias bar indicates an increase in the percentage of studies categorized as “some concerns,” reflecting the consideration of various types of biases and the relative importance of each study. Eight of the twenty tree included articles (35%) exhibited bias related to the randomization process. This finding is problematic, as randomization is essential for minimizing bias and ensuring comparability between treatment groups. The fact that in this domain 6 articles were categorized as having "some concerns" and 2 with "high risk of bias" suggests that this issue is rather significant. Some of the articles raised concerns due to deviations from intended intervention and missing outcome data. Such deviations can significantly impact the validity of the results, as they may lead to inconsistencies in treatment application and hinder the reproducibility of findings. Missing data further complicates interpretations and could skew results, making it difficult to assess the true effects of the interventions evaluated. All articles except one showed a low risk of bias in selection of the reported result. With a single study displaying a risk of bias in this area, it seems to be a relative strength of the included studies. This suggests that, in most cases, researchers appear to have reported results in a transparent and unbiased manner, mitigating potential concerns of selective outcome reporting. None of the studies were associated with bias in measurement of the outcome, indicating that once an outcome was defined, the measurements were consistently applied across studies. This stability in measurement suggests that the outcomes reported can be trusted to reflect the intended constructs reliably, although the initial deviations in intervention could still detract from overall confidence in the findings. The risk of bias assessment presents a mixed landscape among the included studies. While certain aspects demonstrate robustness, significant concerns require careful consideration. The identification of two studies with a "high risk of bias" alongside the eight additional studies raising "some concerns" serves as a call to action for researchers in this field. It underscores the necessity for attentive methodology and transparent reporting in order to enhance the reliability of findings. This assessment is particularly timely as it paves the way for future research endeavors to focus on reducing these biases, ensuring that the resultant evidence is robust. Immunogenicity Overall, the majority of the studies reported on the efficacy of different types of vaccine against the three poliovirus strains (Sabin 1–3). This was confirmed by the increase of antibodies after complete immunization programs and evident from the GMR ranging from 7.1 to 1,172.7 for serotype 1, from 2.0 to 327.2 for serotype 2 and from 12.8 to 590.7 for serotype 3 (titer below 8 are considered non-protective, i.e. negative). Seroconversion rates (SR) consistently varied from 91.5 and 95.1 to 100.0 for serotypes 1 and 3 respectively; for type 2 the lowest values were 45.7, 49.0 and 66.7 (Supplementary Table 1). Primary immunization with 3 IPV doses showed generally high GMRs and SR rates, with sIPV groups exhibiting similar values. Likewise, fractional IPV doses (1/10) exhibited the same immunogenicity as full doses, in some IPV-Al (IM) groups demonstrating even higher values. Comparison of the GMTs in groups administered (s)IPV as opposed to OPV showed, that a single dose of nOPV2 as primary or 1–2 doses as boost immunization is not enough to build immunity against PV2 (SR = 45.7, 49.0 for primary and 66.7 for boost), however a full primary vaccination with tOPV or nOPV2 exhibits GMRs and SR against PV2 similar to (s)IPV. This indicates that all the above-mentioned vaccination schedules are interchangeable and effective. The peak results were recorded among schedules of sIPV with bOPV and combinations of IPV with vaccines against other diseases (DTaP, PRP etc); sIPV-sIPV-bOPV demonstrated the highest antibody levels and 100% seroconversion for serotype 1 and 3, with the GMRs being 1,172.7 and 887.6, respectively. The highest GMR value for serotype 2 was shown by the DTPa-IPV + Hib and is equal to 327.2 (SR also 100%). IPV + RV5 and DTwP-IPV-HB-PRP ~ T had one of the highest GMR scores for all three serotypes (354.6, 117.7, 540.9 and 351.2, 258.8, 573.6, respectively); Clearly sIPV and IPV that are the main vaccines in these schedules, are the reason for such results, but the fact that they were a part of a combination schedule cannot be overlooked: whether DTaP or PRP ∼ T had affected IPV can only be stated after additional research on the matter. In the sIPV-sIPV-bOPV study it was probably the presence of an extra sIPV dose that led to the highest GMRs for ST 1 and 3, since sIPV-bOPV-bOPV had lower antibody rates for these serotypes. It is important to note that the lowest GMRs against type 2 were reported in the sIPV-bOPV-bOPV and IPV-bOPV-bOPV groups (4.6 and 2.0) and D A T A Pa-HBV-IPV/Hib and D B T B Pa-HBV-IPV/Hib groups with values ranging from 3.7 to 13.8 between the 3 serotypes. Both D A T A Pa-HBV-IPV/Hib and D B T B Pa-HBV-IPV/Hib groups belong to the same study, as does the 238 participants DTPa-HBV-IPV/ Hib group, that also has low GMR rates in comparison to groups that were administered the same vaccine but were part of other studies. Taking this into consideration, it could be possible that these particular groups are not sufficient for making any conclusions on the efficacy of the studied vaccines. When it comes to the IPV-bOPV-bOPV group, seroconversion for type 2 was unusually low – only 55.8%. Moreover, in IPV-IPV-bOPV group post-vaccination values were also rather low (GMT = 8.8 and SC = 82.6), hence it is clear that one or two doses of IPV in primary immunization is insufficient for inducing immunity to PV 2. Although the wild polio type 2 is eradicated, such low antibody levels might still pose a threat due to cVDPVs. Thus, as nOPV2 and tOPV showed very similar average GMR rates in comparison to full-dose IPV or sIPV, it is important to keep oral polio vaccine a part of the immunization 55 . Safety assessment An important part of this systematic review was the assessment of the safety of vaccines. The main findings are as follows: vaccines were considered well-tolerated and safe; however, some articles mentioned the need for further research; most common adverse events (AEs) were fever (pyrexia), abnormal crying, diarrhea, vomiting, drowsiness, irritability, injection site sensitivity (tenderness)/pain/erythema, swelling; uncommon were pneumonia, upper/lower respiratory tract infections, bronchiolitis. Most frequently reported AEs were generally consistent with the typical side effects of vaccination 56 . Unfortunately, a comprehensive statistical comparison of AEs was not feasible due to the varying presentation of results across the publications. Some studies provided only general data on the frequency of AEs within specific groups, expressed as percentages. In contrast, other studies offered detailed summaries of individual cases of AEs occurring at different vaccination stages, categorized by specific AE types. Additionally, some articles reported data as the number of patients who developed particular AEs. This inconsistency rendered mathematical processing of the data impossible. Nevertheless, the primary trends identified through the analysis are presented below. Overall, all individual vaccines demonstrated a satisfactory level of safety in the conducted studies. When different individual vaccine types (IPV, sIVP, or tOPV) were compared in a single study, no statistically significant differences were found between the study groups, indicating a similar safety profile. For different doses of IPV-Al there was either an extensive list of AEs, or a complete lack of data, hence, more research is needed to gather data on the safety of aluminum-adjuvanted polio vaccines, given that they provide a strong immune response, are widely used, and are considered to be safe 57 . AE data for IPV-bOPV-bOPV did not contain any differences in comparison to similar vaccination groups, the same applies to D B T B Pa-HBV-IPV/Hib. The general trend for AEs of combinations was similar to single-component vaccines: injection site reactions were most frequent, systemic reactions (like fever, irritability, drowsiness, crying, loss of appetite, vomiting, diarrhea) were all common. It is important to note, that one of the fatal AE occurred in the D A T A Pa -HBV-IPV/Hib (asphyxia and interstitial lung disease) study and the other one in the DTaP-IPV/Hib (infectious shock due to acute bronchopneumonia and congestive heart failure) group. These deaths were not considered as related to the vaccine. The analysis of AEs related to combined vaccines suggests that they tend to have higher rates of local reactions and fever compared to single-component vaccines. This outcome aligns with the main technological challenge of combined vaccines – the administration of multiple antigens simultaneously. While this increases the possibility of local adverse events, multicomponent vaccines are essential to address the growing number of vaccines required for infants and children. These vaccines have the potential to become the key part of any type of immunization against a wide range of diseases 58 . Among the studies, three fatal cases were recorded. The causes of death were asphyxia and interstitial lung disease for one case, septic shock for another, and infectious shock due to acute bronchopneumonia and congestive heart failure for the third. The third case occurred one day after the final vaccine dose, while the first and second occurred 17 and 30 days later, respectively. All three fatalities were considered unrelated to vaccination. 3.7 Baseline GMTs Considering the geographical differences, the baseline (preprimary) GMTs did vary for each poliovirus type across the studies, with the pre-vaccination type 3 titers being considerably lower than type 1 and 2 titers. Highest baseline GMTs: Bangladesh (29.3 for ST1, 56.5 for ST2, 15.1 for ST3), India (31.9 and 53.5 for ST1, 36.2 and 32.5 for ST2, 11.9 for ST 3), Dominican Republic (53.7/ 47.4/ 46.4/ 51.6 for ST2, 13.0 and 12.5 for ST3). Lowest baseline GMTs: Japan (3.58 and 3.35 for ST1, 5.06 and 5.55 for ST2, 2.95/ 2.86/ 3.61 for ST3), South Korea (4.80 and 4.26 for ST1, 4.34 and 4.48 for ST3), Thailand (6.70/ 6.07/ 6.66/ 6.47 for ST 1). Out of the 23 studies 9 were conducted in China, in these articles the baseline GMTs varied from 5.55 to 21.10 for ST 1; from 5.00 to 9.76 for ST2, from 4.34 to 8.08 for ST3. Baseline GMTs for Japan, Bangladesh and India are very abnormal when compared to other values. Although these numbers are clearly noteworthy, it is also important to consider that the analysis included only one study from each of the countries, and more data is needed to establish a correlation between baseline GMT rates and the country of the article’s origin. The samples are too insufficient, especially in comparison to nine different articles conducted in different regions of China, all of which showed very similar GMT rates for ST2 and 3. It is, however, important to note, that India and Bangladesh have been polio-free since 2014 – later, when compared to other countries – and are in direct proximity to Pakistan and Afghanistan, the only endemic regions; a high poverty rate in India is also consistent with pre-disposal to vaccine-preventable diseases. All in all, it is possible that these factors could have led to higher baseline GMT rates in these countries 59 . In contrast, Japan has been polio-free since 1980, largely due to its strong healthcare system, comprehensive vaccination programs, and low exposure to the virus. Low GMTs could indicate that the immunity levels in the general population are relatively high and isolation from endemic regions has reduced the risk of polio cases 60 . Limitations This analysis has some limitations that must be considered in interpreting the results. Firstly, the sample sizes in Table 1 only included participants who fully completed the vaccination, while the AE data came from all participants who received at least one vaccine dose. There was no follow-up AE information for those who have finished the study, leading to inconsistencies between the sample sizes and AE numbers. Secondly, the sample sizes among the 60 immunization groups varied greatly from 10 to 810, with an average number of participants of about 224. As a result, such a range of numbers complicated the comparison process of some vaccination groups, especially their AEs: In some cases, because the samples are so different, it is impossible to make a clear connection between the amount and diversity of side effects and the administered vaccine. Moreover, the articles used different methods of recording and presenting AE data, and some studies did not present that data in a way that was usable. Because of this, a proper comparison and evaluation of the AEs was not possible, which limited the quality of the analysis. Using standardized approaches among studies would help to generate higher-quality analyses. Thirdly, only studies that contained GMT data were included in the review. This resulted in a nearly 5-fold decrease in the number of eligible articles, as there are several other ways to assess the immunogenicity (e.g. geometric mean concentration, median/mean titers, and vaccine efficacy). When measuring the immunity response induced by a vaccine, GMT is most commonly used, as it allows to analyze antibody levels in large groups by giving a good representation of skewed data 61 . That is why in this systematic review the geometric mean titers ratio was calculated from the extracted GMT data in order to analyze the immunogenicity value of various polio vaccines and find the connections or the absence of such between different studies and their findings. It is also important to note that children under six months may have circulating antibodies to polio transmitted from their mothers. Therefore, the higher the polio vaccination coverage in the study region, the more antibodies a child may receive at birth. This could potentially complicate the calculation of SR. Conclusion The systematic review contains an analysis and comparison of the polio vaccines and provides evidence of their immunogenicity and safety. The data is structured and presented in such a way, as to provide a clear overview of all the different immunization approaches and their performances. The study demonstrated that both IPV and sIPV are well-suited for the primary vaccination series, which includes three doses of the vaccine against poliomyelitis. However, a single or double administration is insufficient to establish stable immunity. It is also possible to reduce the dose of the administered antigen when using IPV-Al without compromising the levels of SR and GMR. This approach could potentially decrease the incidence of AEs and enhance compliance among patients in the context of population immunization. Additionally, tOPV is well-suited for establishing primary immunity, showing SR and GMR values comparable to those of IPV and sIPV. In future studies on efficacy and immunogenicity against poliomyelitis, it is essential to provide a more detailed account of the incidence of AEs, which will facilitate a more comprehensive comparison of different types of vaccines. Declarations Ethics approval and consent to participate Not applicable. Consent for publication Not applicable. Availability of data and materials All data generated or analysed during this study are included in this published article and its supplementary information files. Competing interests The authors declare no conflict of interest. The funders had no role in the design of the study; in the collection, analyses, or interpretation of data; in the writing of the manuscript, or in the decision to publish the results. Funding This research was funded by Russian Science Foundation, grant number 23-15-00471. Authors' contributions R.P.T. and L.I.K. conceived and designed the study. M.D.K., A.A.Kh., M.A.V., and A.N.P. conducted literature review and data processing. A.A.S. and A.T. performed data curation. R.P.T., A.A.S., and A.A.Kh. carried out statistical analyses. R.P.T. and M.D.K. performed data visualization. A.A.S., M.D.K., A.A.Kh., and L.I.K. drafted the results section. All authors contributed to data interpretation and discussion. Yu.Yu.I. and D.D.Zh. supervised manuscript preparation and provided critical revisions. D.D.Zh. acquired funding. All authors reviewed, edited, and approved the final manuscript prior to submission. Acknowledgments Not applicable. References Hogle, J. M., Chow, M. & Filman, D. J. Three-Dimensional Structure of Poliovirus at 2.9 Å Resolution. Science 229 , 1358–1365 (1985). Burrill, C. P. et al. Global RNA Structure Analysis of Poliovirus Identifies a Conserved RNA Structure Involved in Viral Replication and Infectivity. J. Virol. (2013) doi:10.1128/jvi.01560-13. Mehndiratta, M. M., Mehndiratta, P. & Pande, R. Poliomyelitis: Historical Facts, Epidemiology, and Current Challenges in Eradication. The Neurohospitalist 4 , 223–229 (2014). Sherris Medical Microbiology: An Introduction to Infectious Diseases . (McGraw-Hill, New York, 2004). Poliomyelitis (polio). https://www.who.int/health-topics/poliomyelitis. GPEI-Wild Poliovirus. https://polioeradication.org/wild-poliovirus/. GPEI-The Vaccines. https://polioeradication.org/about-polio/the-vaccines/. GPEI-Polio this week. https://polioeradication.org/about-polio/polio-this-week/. Zaffran, M., McGovern, M., Hossaini, R., Martin, R. & Wenger, J. The polio endgame: securing a world free of all polioviruses. The Lancet 391 , 11–13 (2018). GPEI-Variant Poliovirus (cVDPV). https://polioeradication.org/about-polio/the-virus/vaccine-derived-polioviruses/. Minor, P. Vaccine-derived poliovirus (VDPV): Impact on poliomyelitis eradication. Vaccine 27 , 2649–2652 (2009). Kew, O. M., Sutter, R. W., Gourville, E. M. de, Dowdle, W. R. & Pallansch, M. A. VACCINE-DERIVED POLIOVIRUSES AND THE ENDGAME STRATEGY FOR GLOBAL POLIO ERADICATION*. Annu. Rev. Microbiol. 59 , 587–635 (2005). Patel, M., Zipursky, S., Orenstein, W., Garon, J. & Zaffran, M. Polio endgame: the global introduction of inactivated polio vaccine. Expert Rev. Vaccines 14 , 749–762 (2015). Sutter, R. W. et al. Immunogenicity of a new routine vaccination schedule for global poliomyelitis prevention: an open-label, randomised controlled trial. The Lancet 386 , 2413–2421 (2015). Asturias, E. J. et al. Humoral and intestinal immunity induced by new schedules of bivalent oral poliovirus vaccine and one or two doses of inactivated poliovirus vaccine in Latin American infants: an open-label randomised controlled trial. The Lancet 388 , 158–169 (2016). Modlin, J. F. & Chumakov, K. Sabin Strain Inactivated Polio Vaccine for the Polio Endgame. J. Infect. Dis. 221 , 504–505 (2020). Hampton, L. M. Cessation of Trivalent Oral Poliovirus Vaccine and Introduction of Inactivated Poliovirus Vaccine — Worldwide, 2016. MMWR Morb. Mortal. Wkly. Rep. 65 , (2016). Khan, M. M. & Ehreth, J. Costs and benefits of polio eradication: a long-run global perspective. Vaccine 21 , 702–705 (2003). Duintjer Tebbens, R. J. et al. Economic analysis of the global polio eradication initiative. Vaccine 29 , 334–343 (2010). GPEI-Vaccine Derived Poliovirus count. https://polioeradication.org/circulating-vaccine-derived-poliovirus-count/. Polio eradication strategy 2022–2026: delivering on a promise. https://www.who.int/publications/i/item/9789240031937. The PRISMA 2020 statement: an updated guideline for reporting systematic reviews | The BMJ. https://doi.org/10.1136/bmj.n71. PROSPERO: An International Register of Systematic Review Protocols: Medical Reference Services Quarterly: Vol 38 , No 2 - Get Access. https://www.tandfonline.com/doi/full/10.1080/02763869.2019.1588072. Cochrane Handbook for Systematic Reviews of Interventions | Wiley Online Books. https://onlinelibrary.wiley.com/doi/book/10.1002/9780470712184. RoB 2: a revised tool for assessing risk of bias in randomised trials | The BMJ. https://www.bmj.com/content/366/bmj.l4898. McGuinness, L. A. & Higgins, J. P. T. Risk‐of‐bias VISualization (robvis): An R package and Shiny web app for visualizing risk‐of‐bias assessments. Res. Synth. Methods 12 , 55–61 (2021). Thelwall, M. & Sud, P. Scopus 1900–2020: Growth in articles, abstracts, countries, fields, and journals. Quant. Sci. Stud. 3 , 37–50 (2022). GPEI-History of Polio. https://polioeradication.org/about-polio/history-of-polio/. van Eck, N. J. & Waltman, L. Software survey: VOSviewer, a computer program for bibliometric mapping. Scientometrics 84 , 523–538 (2010). Eck, N. J. van & Waltman, L. Text mining and visualization using VOSviewer. Preprint at https://doi.org/10.48550/arXiv.1109.2058 (2011). A smart local moving algorithm for large-scale modularity-based community detection | The European Physical Journal B. https://link.springer.com/article/10.1140/epjb/e2013-40829-0#citeas. Rivera, L. et al. Immunogenicity and safety of three aluminium hydroxide adjuvanted vaccines with reduced doses of inactivated polio vaccine (IPV-Al) compared with standard IPV in young infants in the Dominican Republic: a phase 2, non-inferiority, observer-blinded, randomised, and controlled dose investigation trial. Lancet Infect. Dis. 17 , 745–753 (2017). Feng, G. et al. Safety, immunogenicity, and lot-to-lot consistency of a multidose Sabin strain-based inactivated polio vaccine: a phase III, randomized, blinded, positive-control clinical trial in infants aged 2 months. Int. J. Infect. Dis. 130 , 20–27 (2023). Li, R. et al. Primary and booster vaccination with an inactivated poliovirus vaccine (IPV) is immunogenic and well-tolerated in infants and toddlers in China. Vaccine 34 , 1436–1443 (2016). Qiu, J. et al. Immunogenicity and safety evaluation of bivalent types 1 and 3 oral poliovirus vaccine by comparing different poliomyelitis vaccination schedules in China: A randomized controlled non-inferiority clinical trial. Hum. Vaccines Immunother. 13 , 1359–1368 (2017). Capeding, M. R. et al. Safety and Immunogenicity of a New Inactivated Polio Vaccine Made From Sabin Strains: A Randomized, Double-Blind, Active-Controlled, Phase 2/3 Seamless Study. J. Infect. Dis. 226 , 308–318 (2022). Sáez-Llorens, X. et al. Immunogenicity and safety of an adjuvanted inactivated polio vaccine, IPV-Al, following vaccination in children at 2, 4, 6 and at 15–18 months. Vaccine 38 , 3780–3789 (2020). Yan, S. et al. Immunogenicity and safety of different sequential schedules of Sabin strain-based inactivated poliovirus vaccination: A randomized, controlled, open-label, phase IV clinical trial in China. Vaccine 38 , 6274–6279 (2020). Jiang, R. et al. Immunogenicity and safety of the inactivated poliomyelitis vaccine made from Sabin strains in a phase IV clinical trial for the vaccination of a large population. Vaccine 39 , 1463–1471 (2021). Sun, X. et al. Immunogenicity and safety of concomitant administration of the chinese inactivated poliovirus vaccine with the diphtheria-tetanus-acellular pertussis (DTaP) vaccine in children: A multicenter, randomized, non-inferiority, controlled trial. Front. Immunol. 13 , 905634 (2022). Zaman, K. et al. Evaluation of the safety, immunogenicity, and faecal shedding of novel oral polio vaccine type 2 in healthy newborn infants in Bangladesh: a randomised, controlled, phase 2 clinical trial. The Lancet 401 , 131–139 (2023). Ochoge, M. et al. Safety of the novel oral poliovirus vaccine type 2 (nOPV2) in infants and young children aged 1 to <5 years and lot-to-lot consistency of the immune response to nOPV2 in infants in The Gambia: a phase 3, double-blind, randomised controlled trial. The Lancet 403 , 1164–1175 (2024). Rivera Mejía, L. et al. Safety and immunogenicity of shorter interval schedules of the novel oral poliovirus vaccine type 2 in infants: a phase 3, randomised, controlled, non-inferiority study in the Dominican Republic. Lancet Infect. Dis. 24 , 275–284 (2024). Tang, R. et al. A phase Ⅱ, randomized, controlled trial to evaluate the safety and immunogenicity of a Sabin strain-based inactivated polio vaccine. Hum. Vaccines Immunother. 16 , 2641–2648 (2020). Cadorna-Carlos, J., Vidor, E. & Bonnet, M.-C. Randomized controlled study of fractional doses of inactivated poliovirus vaccine administered intradermally with a needle in the Philippines. Int. J. Infect. Dis. 16 , e110–e116 (2012). Sanchez, L. et al. Immunogenicity and Safety of a Hexavalent DTwP-IPV-HB-PRP~T Vaccine Versus Separate DTwP-HB-PRP~T, bOPV, and IPV Vaccines Administered at 2, 4, 6 Months of Age Concomitantly With Rotavirus and Pneumococcal Conjugate Vaccines in Healthy Infants in Thailand. Pediatr. Infect. Dis. J. 42 , 711–718 (2023). Nakayama, T. et al. Immunogenicity and safety of a DTaP-IPV/Hib pentavalent vaccine given as primary and booster vaccinations in healthy infants and toddlers in Japan. J. Infect. Chemother. 26 , 651–659 (2020). Li, Y. et al. Safety, immunogenicity and persistence of immune response to the combined diphtheria, tetanus, acellular pertussis, poliovirus and Haemophilus influenzae type b conjugate vaccine (DTPa-IPV/Hib) administered in Chinese infants. Hum. Vaccines Immunother. 13 , 588–598 (2017). Kang, J. H. et al. The Immunogenicity and Safety of a Combined DTaP-IPV//Hib Vaccine Compared with Individual DTaP-IPV and Hib (PRP~T) Vaccines: a Randomized Clinical Trial in South Korean Infants. J. Korean Med. Sci. 31 , 1383 (2016). Lin, T. Y. et al. A fully liquid diphtheria–tetanus–five component acellular pertussis–inactivated poliomyelitis–Haemophilus influenzae type b conjugate vaccine: immunogenicity and safety of primary vaccination in Taiwanese infants. Int. J. Infect. Dis. 11 , 129–136 (2007). Lim, F. S., Han, H.-H., Jacquet, J.-M. & Bock, H. L. Primary vaccination of infants against hepatitis B can be completed using a combined hexavalent diphtheria-tetanus-acellular pertussis-hepatitis B-inactivated poliomyelitis-Haemophilus influenzae type B vaccine. Ann. Acad. Med. Singapore 36 , 801–806 (2007). Lalwani, S. K. et al. Immunogenicity and safety of 3-dose primary vaccination with combined DTPa-HBV-IPV/Hib in Indian infants. Hum. Vaccines Immunother. 13 , 120–127 (2017). Vesikari, T. et al. Immunogenicity and safety of primary and booster vaccination with 2 investigational formulations of diphtheria, tetanus and Haemophilus influenzae type b antigens in a hexavalent DTPa-HBV-IPV/Hib combination vaccine in comparison with the licensed Infanrix hexa . Hum. Vaccines Immunother. 13 , 1505–1515 (2017). Chen, S. et al. A phase 3 randomized, open-label study evaluating the immunogenicity and safety of concomitant and staggered administration of a live, pentavalent rotavirus vaccine and an inactivated poliomyelitis vaccine in healthy infants in China. Hum. Vaccines Immunother. 20 , 2324538 (2024). Voorman, A. et al. Analysis of population immunity to poliovirus following cessation of trivalent oral polio vaccine. Vaccine 41 Suppl 1 , A85–A92 (2023). Iqbal, S. et al. Preparation for global introduction of inactivated poliovirus vaccine: safety evidence from the US Vaccine Adverse Event Reporting System, 2000–12. Lancet Infect. Dis. 15 , 1175–1182 (2015). Hogenesch, H. Mechanism of immunopotentiation and safety of aluminum adjuvants. Front. Immunol. 3 , 406 (2012). Skibinski, D. A., Baudner, B. C., Singh, M. & O’Hagan, D. T. Combination Vaccines. J. Glob. Infect. Dis. 3 , 63 (2011). Jl, M. Inequity in childhood immunization in India: a systematic review. Indian Pediatr. 49 , (2012). Toizumi, M., Takamatsu, M., Toda, K. & Horikoshi, Y. Progresses Toward Polio Eradication in Asian Countries: Its History and Japan’s Contributions. Pediatr. Infect. Dis. J. 43 , e347–e353 (2024). Reverberi, R. The statistical analysis of immunohaematological data. Blood Transfus. 6 , 37–45 (2008). Additional Declarations No competing interests reported. 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As a division of Research Square Company, we’re committed to making research communication faster, fairer, and more useful. We do this by developing innovative software and high quality services for the global research community. Our growing team is made up of researchers and industry professionals working together to solve the most critical problems facing scientific publishing. Also discoverable on Platform About Our Team In Review Editorial Policies Advisory Board Help Center Resources Author Services Accessibility API Access RSS feed Manage Cookie Preferences © Research Square 2026 | ISSN 2693-5015 (online) Privacy Policy Terms of Service Do Not Sell My Personal Information {"props":{"pageProps":{"initialData":{"identity":"rs-6913898","acceptedTermsAndConditions":true,"allowDirectSubmit":false,"archivedVersions":[],"articleType":"Research Article","associatedPublications":[],"authors":[{"id":477697185,"identity":"ff1c1b69-2bd2-42df-a3cd-d3545dea3df5","order_by":0,"name":"Roman P. 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Created by VOSviewer \u003csup\u003e29, 30, 31\u003c/sup\u003e.\u003c/p\u003e","description":"","filename":"1.png","url":"https://assets-eu.researchsquare.com/files/rs-6913898/v1/ea80d90a34a013854d50823c.png"},{"id":85755730,"identity":"4d3a3c1f-30a4-4bbf-a1c9-1e93e8da8634","added_by":"auto","created_at":"2025-07-01 10:45:40","extension":"png","order_by":2,"title":"Figure 2","display":"","copyAsset":false,"role":"figure","size":162766,"visible":true,"origin":"","legend":"\u003cp\u003ePRISMA flowchart of the search and selection process of the articles.\u003c/p\u003e","description":"","filename":"2.png","url":"https://assets-eu.researchsquare.com/files/rs-6913898/v1/e225b535db1ac56b767bd429.png"},{"id":85757221,"identity":"c92f02fc-83a8-4456-9d07-19b1651e4d30","added_by":"auto","created_at":"2025-07-01 10:53:40","extension":"png","order_by":3,"title":"Figure 3","display":"","copyAsset":false,"role":"figure","size":247360,"visible":true,"origin":"","legend":"\u003cp\u003ea. Risk of bias summary “traffic light”\u003c/p\u003e\n\u003cp\u003eb. Weighted bar plot\u003c/p\u003e","description":"","filename":"3.png","url":"https://assets-eu.researchsquare.com/files/rs-6913898/v1/5c5af5d3ed3882de25f00e1a.png"},{"id":95040456,"identity":"acac376d-4d2f-42ee-9369-e5e48129dbb0","added_by":"auto","created_at":"2025-11-03 16:08:59","extension":"pdf","order_by":0,"title":"","display":"","copyAsset":false,"role":"manuscript-pdf","size":2096325,"visible":true,"origin":"","legend":"","description":"","filename":"manuscript.pdf","url":"https://assets-eu.researchsquare.com/files/rs-6913898/v1/3f6b7155-d861-4377-b04e-42bebf58cb3a.pdf"},{"id":85755736,"identity":"62be7f61-ca9e-4350-86c5-8d289fcc6014","added_by":"auto","created_at":"2025-07-01 10:45:40","extension":"pdf","order_by":0,"title":"","display":"","copyAsset":false,"role":"supplement","size":148442,"visible":true,"origin":"","legend":"","description":"","filename":"PolioVaccinesSupplTableS1.pdf","url":"https://assets-eu.researchsquare.com/files/rs-6913898/v1/3ef146ac34385a7f0c419dce.pdf"}],"financialInterests":"No competing interests reported.","formattedTitle":"Immunogenicity and Safety of Polio Vaccines in Infants: A Systematic Review of Randomized Clinical Trials","fulltext":[{"header":"Introduction","content":"\u003cp\u003e \u003cdiv class=\"BlockQuote\"\u003e \u003cp\u003ePoliomyelitis is a highly contagious disease that can be contracted by an unvaccinated person of any age but disease more often occurs in children under 5 years of age. The causative agent of this disease is poliovirus, a small, non-enveloped virus containing a single-stranded positive-sense RNA genome, about 7,500 nucleotides long, enclosed in a protein capsid. The capsid is made up of 60 protomers composed of four viral proteins (VP 1\u0026ndash;4) arranged in icosahedral symmetry, with VP 1\u0026ndash;3 creating antigenic sites for receptor and antibodies to bind. Based on the slight differences in the capsid structure, three types of polioviruses (type 1, 2 and 3) are distinguished \u003csup\u003e\u003cspan citationid=\"CR1\" class=\"CitationRef\"\u003e1\u003c/span\u003e,\u003cspan citationid=\"CR2\" class=\"CitationRef\"\u003e2\u003c/span\u003e,\u003cspan citationid=\"CR3\" class=\"CitationRef\"\u003e3\u003c/span\u003e,\u003cspan citationid=\"CR4\" class=\"CitationRef\"\u003e4\u003c/span\u003e\u003c/sup\u003e.\u003c/p\u003e \u003cp\u003eThere is no cure for polio, and the nerve damage and paralysis that it causes can be permanent or even fatal \u003csup\u003e\u003cspan citationid=\"CR5\" class=\"CitationRef\"\u003e5\u003c/span\u003e\u003c/sup\u003e. The only way of preventing the disease is through vaccination, which has proven to be effective against all 3 types of poliovirus. The main two forms of polio vaccine are oral polio vaccine (OPV) and inactivated polio vaccine (IPV) \u003csup\u003e\u003cspan citationid=\"CR6\" class=\"CitationRef\"\u003e6\u003c/span\u003e,\u003cspan citationid=\"CR7\" class=\"CitationRef\"\u003e7\u003c/span\u003e\u003c/sup\u003e. Both OPV and IPV have been widely applied since the 1950-60s and continue to be a crucial part of the Global Polio Eradication Initiative (GPEI)\u0026ndash; since its launch in 1988 polio incidence has globally decreased by over 99%, leaving only the wild polioviruses type 1 still endemic in Pakistan and Afghanistan \u003csup\u003e\u003cspan citationid=\"CR5\" class=\"CitationRef\"\u003e5\u003c/span\u003e,\u003cspan citationid=\"CR8\" class=\"CitationRef\"\u003e8\u003c/span\u003e,\u003cspan citationid=\"CR9\" class=\"CitationRef\"\u003e9\u003c/span\u003e\u003c/sup\u003e.\u003c/p\u003e \u003cp\u003eIt is important to mention that, despite OPV inducing good intestinal immunity and being generally safe, the live attenuated polioviruses it contains can cause vaccine-associated paralytic poliomyelitis (VAPP) and mutate into circulating vaccine-derived polioviruses (cVDPV) able to cause polio cases and outbreaks \u003csup\u003e\u003cspan citationid=\"CR10\" class=\"CitationRef\"\u003e10\u003c/span\u003e,\u003cspan citationid=\"CR11\" class=\"CitationRef\"\u003e11\u003c/span\u003e,\u003cspan citationid=\"CR12\" class=\"CitationRef\"\u003e12\u003c/span\u003e\u003c/sup\u003e. Polio vaccine virus type 2 is mostly associated with VDPV2 and is responsible for most outbreaks. For this reason, global switch from trivalent OPV types 1, 2 and 3 to bivalent OPV types 1 and 3 was performed in 2016. This process included a transition to vaccination schedules that include IPV to maintain immunity to polioviruses type 2. Moreover, IPV it contains an inactivated virus and carries no risk of VAPP or VDPV \u003csup\u003e\u003cspan citationid=\"CR13\" class=\"CitationRef\"\u003e13\u003c/span\u003e,\u003cspan citationid=\"CR14\" class=\"CitationRef\"\u003e14\u003c/span\u003e,\u003cspan citationid=\"CR15\" class=\"CitationRef\"\u003e15\u003c/span\u003e,\u003cspan citationid=\"CR16\" class=\"CitationRef\"\u003e16\u003c/span\u003e,\u003cspan citationid=\"CR17\" class=\"CitationRef\"\u003e17\u003c/span\u003e\u003c/sup\u003e.\u003c/p\u003e \u003cp\u003eAlso, due to the increasing cost of GPEI, the question of its necessity arises, given the low number of polio cases and the nearly global routine immunization. Nevertheless, continuing the program is critical, and not only to ensure vaccination coverage, but also because it is a cost-effective decision with substantial long-term benefits that far outweigh the expenses. The cost of health care saved by preventing polio and related cases of paralysis is more than two to three times higher, than the cost of polio eradication in the long term. Over the years 1970\u0026ndash;2050, polio vaccination will prevent about 42\u0026nbsp;million polio cases, and thus prevent about 855,000 deaths and more than 4\u0026nbsp;million paralysis cases\u003csup\u003e\u003cspan citationid=\"CR18\" class=\"CitationRef\"\u003e18\u003c/span\u003e\u003c/sup\u003e. In terms of disability-adjusted life years (DALYs), vaccination and polio eradication will save about 39.5\u0026nbsp;million years by the year 2050 \u003csup\u003e18,19\u003c/sup\u003e.\u003c/p\u003e \u003cp\u003eIn recent years, low immunization coverage hinders the GPEI progress. Between 2021 and 2024 there were 2,406 paralysis cases recorded in regions such as parts of Africa, Yemen, and Indonesia, attributed to newly formed cVDPVs of all three types \u003csup\u003e\u003cspan citationid=\"CR20\" class=\"CitationRef\"\u003e20\u003c/span\u003e\u003c/sup\u003e. Moreover, in Afghanistan and Pakistan endemic transmission of wild poliovirus type 1 (WPV1) continues with increasing number of polio cases: in 2024 the total 99 cases were recorded in the area \u003csup\u003e\u003cspan citationid=\"CR10\" class=\"CitationRef\"\u003e10\u003c/span\u003e, \u003cspan citationid=\"CR21\" class=\"CitationRef\"\u003e21\u003c/span\u003e\u003c/sup\u003e.\u003c/p\u003e \u003cp\u003eMoreover, this decline in vaccination has been intensified by numerous cases of misinformation and anti-vaccine activism that have emerged in the last couple of years. The most common misinformation pieces claimed that vaccines were unsafe and that they could cause other diseases. Battling such accusations by providing grounded proof is necessary, and is now more urgent than ever, as the GPEI sets 2026 as the year for complete polio eradication.\u003c/p\u003e \u003cp\u003eThe possibility of virus breakouts and further spread of misinformation on a wider scale is putting at risk the GPEI goal, hence it is extremely important to maintain high vaccination rates and to raise awareness of the importance of vaccination. Which is why the aim of this review is to provide a comprehensive summary of data regarding various immunization methods to demonstrate the immunogenicity and safety of existing polio vaccines.\u003c/p\u003e \u003c/div\u003e \u003c/p\u003e"},{"header":"Materials and Methods","content":"\u003cdiv id=\"Sec3\" class=\"Section2\"\u003e \u003ch2\u003eStudy design\u003c/h2\u003e \u003cp\u003e\u003cdiv class=\"BlockQuote\"\u003e\u003cp\u003eThe design of this systematic review was conducted by the Preferred Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA) guidelines \u003csup\u003e\u003cspan citationid=\"CR22\" class=\"CitationRef\"\u003e22\u003c/span\u003e\u003c/sup\u003e. A protocol for this study has been registered on PROSPERO \u003csup\u003e\u003cspan citationid=\"CR23\" class=\"CitationRef\"\u003e23\u003c/span\u003e\u003c/sup\u003e under ID CRD42024574830 in August 2024 .\u003c/p\u003e\u003c/div\u003e\u003c/p\u003e \u003c/div\u003e\n\u003ch3\u003eData sources\u003c/h3\u003e\n\u003cp\u003e \u003cdiv class=\"BlockQuote\"\u003e \u003cp\u003eA systematic search of papers was conducted using the following databases: PubMed/MEDLINE, Google Scholar, and eLibrary.\u003c/p\u003e \u003c/div\u003e \u003c/p\u003e\n\u003ch3\u003eSearch strategy\u003c/h3\u003e\n\u003cp\u003e \u003cdiv class=\"BlockQuote\"\u003e \u003cp\u003eThe search strategy in English combined the following terms: (poliomyelitis OR (infantile AND paralysis) OR \u0026ldquo;essential paralysis\u0026rdquo; OR \u0026ldquo;Heine-Medin disease\u0026rdquo; OR tephromyelitis OR polio) AND (immunogen* OR efficacy OR seroconversion) AND (vaccin* OR poliovaccine). In Russian the equal terms were used.\u003c/p\u003e \u003c/div\u003e \u003c/p\u003e\n\u003ch3\u003eInclusion and exclusion criteria\u003c/h3\u003e\n\u003cp\u003e \u003cdiv class=\"BlockQuote\"\u003e \u003cp\u003eThe inclusion and exclusion criteria were based on the PICOS principles \u003csup\u003e\u003cspan citationid=\"CR24\" class=\"CitationRef\"\u003e24\u003c/span\u003e\u003c/sup\u003e. They are summarized in Table\u0026nbsp;\u003cspan refid=\"Tab1\" class=\"InternalRef\"\u003e1\u003c/span\u003e.\u003c/p\u003e \u003c/div\u003e \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\u003eInclusion and exclusion criteria.\u003c/p\u003e \u003c/div\u003e \u003c/caption\u003e \u003ccolgroup cols=\"3\"\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 \u003cthead\u003e \u003ctr\u003e \u003cth align=\"left\" colname=\"c1\"\u003e \u003cp\u003eCriteria\u003c/p\u003e \u003c/th\u003e \u003cth align=\"left\" colname=\"c2\"\u003e \u003cp\u003eInclusion\u003c/p\u003e \u003c/th\u003e \u003cth align=\"left\" colname=\"c3\"\u003e \u003cp\u003eExclusion\u003c/p\u003e \u003c/th\u003e \u003c/tr\u003e \u003c/thead\u003e \u003ctbody\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003ePopulation\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003eInfants (age from birth to 1 year)\u003c/p\u003e \u003cp\u003eMales or females\u003c/p\u003e \u003cp\u003eHealthy\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003eAny illness or medical condition\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eIntervention\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003eImmunization\u003c/p\u003e \u003cp\u003e by any polio vaccine\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003eAbsence of immunization \u003c/p\u003e \u003cp\u003eby any polio vaccine\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eControl\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colspan=\"2\" nameend=\"c3\" namest=\"c2\"\u003e \u003cp\u003eThe presence of control group in analyzed publications\u003c/p\u003e \u003cp\u003e is not necessary\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eOutcome measure(s)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003eGeometric mean \u003c/p\u003e \u003cp\u003eneutralizing antibody titers (GMT) before immunization \u003c/p\u003e \u003cp\u003eand at the day 21\u0026ndash;31 \u003c/p\u003e \u003cp\u003eafter immunization\u003c/p\u003e \u003cp\u003eData separated depending \u003c/p\u003e \u003cp\u003eon the polio serotype\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003eNo GMT data\u003c/p\u003e \u003cp\u003e before immunization\u003c/p\u003e \u003cp\u003eNo GMT data at the day 21\u0026ndash;31 \u003c/p\u003e \u003cp\u003eafter immunization\u003c/p\u003e \u003cp\u003eNo serotype details\u003c/p\u003e \u003cp\u003e for GMT data\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eStudy design\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003eRandomized clinical trials\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003eStudy of any other design\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003c/tbody\u003e \u003c/colgroup\u003e \u003c/table\u003e\u003c/div\u003e \u003c/p\u003e \u003cp\u003e \u003cdiv class=\"BlockQuote\"\u003e \u003cp\u003eOnly papers that provided the full text in English or Russian were included in the systematic review.\u003c/p\u003e \u003c/div\u003e \u003c/p\u003e\n\u003ch3\u003eData collection\u003c/h3\u003e\n\u003cp\u003e \u003cdiv class=\"BlockQuote\"\u003e \u003cp\u003eAll papers obtained from the databases were recorded in cloudified table. Duplicates were removed prior to screening. Two researchers (A.A.Kh. and M.A.V.) independently evaluated the article set according to including and excluding criteria, based on the titles and abstracts. In case of disagreement, the third researcher (Yu.Yu.I.) served as a referee. Then full texts of selected studies were assessed for eligibility.\u003c/p\u003e \u003c/div\u003e \u003c/p\u003e \u003cdiv id=\"Sec8\" class=\"Section2\"\u003e \u003ch2\u003eData extraction\u003c/h2\u003e \u003cp\u003e \u003cdiv class=\"BlockQuote\"\u003e \u003cp\u003eTwo reviewers (A.A.Kh. and M.A.V.) independently performed the data extraction. The following data were in focus: number of immunized patients, country of study; dose, timing, formulation, administration, combination, and valency of vaccine; antibody titer; side effects (number of cases), poliomyelitis cases (number of cases); bibliographical details.\u003c/p\u003e \u003c/div\u003e \u003c/p\u003e \u003c/div\u003e \u003cdiv id=\"Sec9\" class=\"Section2\"\u003e \u003ch2\u003eData analysis\u003c/h2\u003e \u003cp\u003e \u003cdiv class=\"BlockQuote\"\u003e \u003cp\u003eThree researchers (R.P.T., A.A.S., and A.A.Kh.) performed the formal analysis of extracted data. To standardize the immunogenicity value of polio vaccines in selected studies the geometric mean titers ratio (GMR) was calculated, using the following formula:\u003c/p\u003e \u003c/div\u003e \u003cdiv id=\"Equ1\" class=\"Equation\"\u003e \u003cdiv format=\"TEX\" class=\"mathdisplay\" id=\"FileID_Equ1\" name=\"EquationSource\"\u003e\n$$\\:GMR=\\:\\frac{{GMT}_{n}}{{GMT}_{0}}$$\u003c/div\u003e \u003cdiv class=\"EquationNumber\"\u003e1\u003c/div\u003e\u003c/div\u003e,\u003c/p\u003e \u003cp\u003e\u003cdiv class=\"BlockQuote\"\u003e\u003cp\u003ewhere GMT\u003csub\u003e0\u003c/sub\u003e is the GMT value before the immunization and GMT\u003csub\u003en\u003c/sub\u003e is the GMT value at the day 21\u0026ndash;31 after the immunization.\u003c/p\u003e\u003cp\u003e The obtained GMR values, number side effect cases, and number of were combined based on the types of vaccines and patients\u0026rsquo; characteristics. To evaluate the significance of differences between the groups in the analyzed parameters, the mean values and the confidence intervals were calculated (\u003cem\u003ep\u003c/em\u003e\u0026thinsp;=\u0026thinsp;0.05).\u003c/p\u003e\u003c/div\u003e\u003c/p\u003e \u003c/div\u003e\n\u003ch3\u003eRisk of Bias assessment\u003c/h3\u003e\n\u003cp\u003e\u003cdiv class=\"BlockQuote\"\u003e\u003cp\u003eThe included studies were independently assessed by the two researchers (M.D.K. and A.N.P.), using the version 2 of the Risk of Bias (RoB 2) tool \u003csup\u003e\u003cspan citationid=\"CR25\" class=\"CitationRef\"\u003e25\u003c/span\u003e\u003c/sup\u003e. The quality of evidence for the primary outcomes was evaluated via following bias domains: randomization process, deviations of intended interventions, missing outcome data, measurement of the outcome, and selection of the reported results. In case of discrepancies, they were resolved by a tiebreaker reviewer (L.I.K.). To visualize the results of RoB assessment, the ROBVIS tool was applied \u003csup\u003e\u003cspan citationid=\"CR26\" class=\"CitationRef\"\u003e26\u003c/span\u003e\u003c/sup\u003e. To evaluate the publication biases, the funnel plots were built in case of enough volume of data (\u003cem\u003en\u003c/em\u003e\u0026thinsp;\u0026ge;\u0026thinsp;10).\u003c/p\u003e\u003c/div\u003e\u003c/p\u003e"},{"header":"Results and Discussion","content":"\u003cdiv id=\"Sec12\" class=\"Section2\"\u003e\n \u003ch2\u003eGeneral outlook on the scientific landscape\u003c/h2\u003e\n \u003cdiv class=\"BlockQuote\"\u003e\n \u003cp\u003eSince 1984 the number of articles on polio vaccines has visibly increased. Over the past 10 years has reached about 60 articles on average per year (Fig.\u0026nbsp;1a). These data deposited in PubMed were used to build a bibliometric network based on keywords co-occurring with the terms \u0026ldquo;poliovirus\u0026rdquo; and \u0026ldquo;vaccine\u0026rdquo; in articles (Fig.\u0026nbsp;1b). The terms \u0026ldquo;humans\u0026rdquo;, \u0026ldquo;infant\u0026rdquo;, \u0026ldquo;male\u0026rdquo;, \u0026ldquo;female\u0026rdquo;, \u0026ldquo;poliovirus vaccines, inactivate\u0026rdquo;, \u0026ldquo;poliovirus vaccines, oral\u0026rdquo;, and \u0026ldquo;antibodies, viral\u0026rdquo; are the most frequently used, which is indicated by their bubble size.\u003c/p\u003e\n \u003cp\u003eWe also looked at the general publication trends of the twentieth century, and it was the middle of the 1980s when the number of studies on polio vaccines has begun to increase. The overall scientific background at the time did not experience any sudden changes while continuously growing since the late 1940s \u003csup\u003e\u003cspan class=\"CitationRef\"\u003e27\u003c/span\u003e\u003c/sup\u003e. Therefore, such activity is most likely correlates with the global effort to eradicate polio that had begun in 1985 with the start of the PolioPlus initiative and was followed by the launch of the Global Polio Eradication Initiative (GPEI) in 1988. All national immunizations and polio monitoring campaigns were inevitably accompanied by a large volume of publications on these programs and their results. Clearly, the 1980s has become a turning point in the fight against polio, raising the global interest in collaborative polio eradication efforts that continue to be ongoing today \u003csup\u003e\u003cspan class=\"CitationRef\"\u003e28\u003c/span\u003e\u003c/sup\u003e. It is also noteworthy, that there has been a shift in interest towards the immunogenicity of the polio vaccine in the recent years (Fig.\u0026nbsp;1c) that confirms the significance of the systematic review.\u003c/p\u003e\n \u003cp\u003eIn order to fully estimate the relevance of the review, a primary evaluation of the PROSPERO search results on the immunogenicity of polio vaccines was performed and showed that our analysis is not only relevant due to the lack of similar articles on polio vaccine, but also unique in the variety of different vaccines that were compared and assessed.\u003c/p\u003e\n \u003c/div\u003e\n\u003c/div\u003e\n\u003cdiv id=\"Sec14\" class=\"Section2\"\u003e\n \u003ch2\u003eProcess of collection and selection of the studies\u003c/h2\u003e\n \u003cdiv class=\"BlockQuote\"\u003e\n \u003cp\u003eA total of 1,845 articles were identified through the search strategies of Pubmed/MEDLINE, eLibrary and GoogleScholar. Before the screening, 102 duplicates were removed. After the first screening 1,600 articles did not meet the inclusion criteria based on their titles and abstracts, and therefore were excluded. After the second screening an additional of 48 articles were removed. During the final screening 75 records were excluded due to the following reasons: the absence of blood samples collection on days 21\u0026ndash;31 after the last vaccination (\u003cem\u003en\u003c/em\u003e\u0026thinsp;=\u0026thinsp;37), patients are older than 1 year of age (\u003cem\u003en\u003c/em\u003e\u0026thinsp;=\u0026thinsp;3), use of median titers (\u003cem\u003en\u003c/em\u003e\u0026thinsp;=\u0026thinsp;19), no data on GMT (\u003cem\u003en\u003c/em\u003e\u0026thinsp;=\u0026thinsp;6), lack of initial data on antibody titers (\u003cem\u003en\u003c/em\u003e\u0026thinsp;=\u0026thinsp;6), other reasons (\u003cem\u003en\u003c/em\u003e\u0026thinsp;=\u0026thinsp;4). The total of 23 studies were included in this systematic review. The collection and selection process are illustrated in the PRISMA flow diagram (Fig. \u003cspan class=\"InternalRef\"\u003e2\u003c/span\u003e).\u003c/p\u003e\n \u003c/div\u003e\n\u003c/div\u003e\n\u003cdiv id=\"Sec15\" class=\"Section2\"\u003e\n \u003ch2\u003e3.3 Qualitative synthesis\u003c/h2\u003e\n \u003cp\u003eA total of 15,052 participants were analyzed in the 23 included studies. 1,065 infants were assigned to the groups administered only IPV (Salk vaccine) \u003csup\u003e\u003cspan class=\"CitationRef\"\u003e32\u003c/span\u003e, \u003cspan class=\"CitationRef\"\u003e33\u003c/span\u003e, \u003cspan class=\"CitationRef\"\u003e34\u003c/span\u003e, \u003cspan class=\"CitationRef\"\u003e35\u003c/span\u003e,\u003cspan class=\"CitationRef\"\u003e36\u003c/span\u003e\u003c/sup\u003e, another 969 infants to the groups which received IPV-Al (aluminium hydroxide-adjuvanted IPV) \u003csup\u003e\u003cspan class=\"CitationRef\"\u003e32\u003c/span\u003e, \u003cspan class=\"CitationRef\"\u003e37\u003c/span\u003e\u003c/sup\u003e as part of their immunization. A number of studies included administration of sIPV (IPV from Sabin strains) to a total of 3,406 infants \u003csup\u003e\u003cspan class=\"CitationRef\"\u003e33\u003c/span\u003e, \u003cspan class=\"CitationRef\"\u003e36\u003c/span\u003e, \u003cspan class=\"CitationRef\"\u003e38\u003c/span\u003e, \u003cspan class=\"CitationRef\"\u003e39\u003c/span\u003e, \u003cspan class=\"CitationRef\"\u003e40\u003c/span\u003e,\u003c/sup\u003e. The efficacy of OPV (nOPV2, bOPV, tOPV) against polio strains was assessed in 3,738 participants \u003csup\u003e41 42 34 35 43\u003c/sup\u003e. One of the studies evaluated the effectiveness of a combined IPV and OPV (bOPV or tOPV) vaccination with 563 recipients \u003csup\u003e\u003cspan class=\"CitationRef\"\u003e35\u003c/span\u003e\u003c/sup\u003e, and another trial was conducted with 374 recipients and the combination of sIPV and bOPV \u003csup\u003e\u003cspan class=\"CitationRef\"\u003e38\u003c/span\u003e\u003c/sup\u003e. The majority of participants in the amount of 4,345 were administered some kind of combination of IPV \u003csup\u003e\u003cspan class=\"CitationRef\"\u003e37\u003c/span\u003e, \u003cspan class=\"CitationRef\"\u003e44\u003c/span\u003e, \u003cspan class=\"CitationRef\"\u003e45\u003c/span\u003e, 46 47 48 49 50 51 52 53\u003c/sup\u003e with DTaP/DTwP (diphtheria-tetanus-acellular/ whole-cell pertussis vaccine), Hib (\u003cem\u003eHaemophilus influenzae\u003c/em\u003e type b), PRP \u0026sim; T (polyribose ribitol phosphate conjugated to tetanus protein), HBV (hepatitis B vaccine) or RV5 (pentavalent rotavirus vaccine)\u003csup\u003e\u003cspan class=\"CitationRef\"\u003e54\u003c/span\u003e\u003c/sup\u003e; combined vaccines with sIPV were administered to 592 participants \u003csup\u003e\u003cspan class=\"CitationRef\"\u003e40\u003c/span\u003e, \u003cspan class=\"CitationRef\"\u003e44\u003c/span\u003e\u003c/sup\u003e. In a single study 219 participants were administered a combination of DTwP-HB-Hib and bOPV with IPV \u003csup\u003e\u003cspan class=\"CitationRef\"\u003e46\u003c/span\u003e\u003c/sup\u003e.\u003c/p\u003e\n \u003cdiv class=\"BlockQuote\"\u003e\n \u003cp\u003eThe intervention method was either injection (intramuscular (IM), intradermal (ID), sequential (SC)) or oral administration (\u003cem\u003eper os\u003c/em\u003e). In all of the studies a full dose of OPV was administered, IPV doses varied from a full to a reduced dose (1/\u003cem\u003en\u003c/em\u003e, \u003cem\u003en\u003c/em\u003e\u0026thinsp;=\u0026thinsp;3, 5, and 10) with one of the trials assessing the efficacy of a low, medium, and high dose.\u003c/p\u003e\n \u003cp\u003eThe findings from the 23 articles are summarized in Supplementary Table 1. For the same vaccines administered in more than 1 study the mean GMR was calculated (95% CI) and presented in Table\u0026nbsp;\u003cspan class=\"InternalRef\"\u003e2\u003c/span\u003e. Due to lack of clarification on the exact vaccines administered in studies with IPV or sIPV when trial subjects were allowed to be vaccinated with \u0026ldquo;other vaccines\u0026rdquo; according to the routine immunization schedule, these groups were not included in the mean GMR table.\u003c/p\u003e\n \u003c/div\u003e\n \u003cdiv class=\"gridtable\"\u003e\u0026nbsp;\u003ctable id=\"Tab2\" border=\"1\"\u003e\n \u003ccaption language=\"En\"\u003e\n \u003cdiv class=\"CaptionNumber\"\u003eTable 2\u003c/div\u003e\n \u003cdiv class=\"CaptionContent\"\u003e\n \u003cp\u003eStatistical processing of data from several articles.\u003c/p\u003e\n \u003c/div\u003e\n \u003c/caption\u003e\n \u003ccolgroup cols=\"6\"\u003e\u003c/colgroup\u003e\n \u003cthead\u003e\n \u003ctr\u003e\n \u003cth align=\"left\" rowspan=\"2\"\u003e\n \u003cp\u003eType\u003c/p\u003e\n \u003cp\u003eof polio\u003c/p\u003e\n \u003cp\u003evaccine\u003c/p\u003e\n \u003c/th\u003e\n \u003cth align=\"left\" rowspan=\"2\"\u003e\n \u003cp\u003eSample size\u003c/p\u003e\n \u003c/th\u003e\n \u003cth align=\"left\" rowspan=\"2\"\u003e\n \u003cp\u003eDosage form\u003c/p\u003e\n \u003c/th\u003e\n \u003cth align=\"left\" colspan=\"3\"\u003e\n \u003cp\u003eAverage GMR, IU\u003c/p\u003e\n \u003c/th\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003cth align=\"left\"\u003e\n \u003cp\u003eSerotype I\u003c/p\u003e\n \u003c/th\u003e\n \u003cth align=\"left\"\u003e\n \u003cp\u003eSerotype II\u003c/p\u003e\n \u003c/th\u003e\n \u003cth align=\"left\"\u003e\n \u003cp\u003eSerotype III\u003c/p\u003e\n \u003c/th\u003e\n \u003c/tr\u003e\n \u003c/thead\u003e\n \u003ctbody\u003e\n \u003ctr\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003eIPV\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"char\"\u003e\n \u003cp\u003e1,065\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003eINJ\u003c/p\u003e\n \u003cp\u003e1.0\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"char\"\u003e\n \u003cp\u003e83.08\u0026thinsp;\u0026plusmn;\u0026thinsp;86.90\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"char\"\u003e\n \u003cp\u003e33.60\u0026thinsp;\u0026plusmn;\u0026thinsp;18.78\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"char\"\u003e\n \u003cp\u003e166.30\u0026thinsp;\u0026plusmn;\u0026thinsp;109.12\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003esIPV\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"char\"\u003e\n \u003cp\u003e3,406\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003eINJ\u003c/p\u003e\n \u003cp\u003e1.0\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"char\"\u003e\n \u003cp\u003e234.35\u0026thinsp;\u0026plusmn;\u0026thinsp;175.25\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"char\"\u003e\n \u003cp\u003e44.04\u0026thinsp;\u0026plusmn;\u0026thinsp;12.58\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"char\"\u003e\n \u003cp\u003e163.13\u0026thinsp;\u0026plusmn;\u0026thinsp;76.94\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003etOPV\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"char\"\u003e\n \u003cp\u003e374\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003eOral\u003c/p\u003e\n \u003cp\u003e1.0\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"char\"\u003e\n \u003cp\u003e257.55\u0026thinsp;\u0026plusmn;\u0026thinsp;203.15\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"char\"\u003e\n \u003cp\u003e50.75\u0026thinsp;\u0026plusmn;\u0026thinsp;28.13\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"char\"\u003e\n \u003cp\u003e88.05\u0026thinsp;\u0026plusmn;\u0026thinsp;13.03\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003eDTaP-IPV/Hib\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"char\"\u003e\n \u003cp\u003e651\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003eINJ\u003c/p\u003e\n \u003cp\u003e1.0\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"char\"\u003e\n \u003cp\u003e129.27\u0026thinsp;\u0026plusmn;\u0026thinsp;61.72\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"char\"\u003e\n \u003cp\u003e83.84\u0026thinsp;\u0026plusmn;\u0026thinsp;17.42\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"char\"\u003e\n \u003cp\u003e247.87\u0026thinsp;\u0026plusmn;\u0026thinsp;49.98\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003eDTPa-HBV-IPV/ Hib\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"char\"\u003e\n \u003cp\u003e510\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003eINJ\u003c/p\u003e\n \u003cp\u003e1.0\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"char\"\u003e\n \u003cp\u003e36.45\u0026thinsp;\u0026plusmn;\u0026thinsp;39.10\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"char\"\u003e\n \u003cp\u003e42.50\u0026thinsp;\u0026plusmn;\u0026thinsp;32.54\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"char\"\u003e\n \u003cp\u003e152.10\u0026thinsp;\u0026plusmn;\u0026thinsp;71.73\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003c/tbody\u003e\n \u003ctfoot\u003e\n \u003ctr\u003e\n \u003ctd colspan=\"6\"\u003e*data are presented as average GMR\u0026thinsp;\u0026plusmn;\u0026thinsp;half-width of the confidence interval (\u003cem\u003ep\u003c/em\u003e\u0026thinsp;\u0026lt;\u0026thinsp;0.05)\u003c/td\u003e\n \u003c/tr\u003e\n \u003c/tfoot\u003e\n \u003c/table\u003e\n \u003c/div\u003e\n\u003c/div\u003e\n\u003cdiv id=\"Sec16\" class=\"Section2\"\u003e\n \u003ch2\u003eRisk of Bias\u003c/h2\u003e\n \u003cdiv class=\"BlockQuote\"\u003e\n \u003cp\u003ePossible forms of bias were assessed according to the RoB 2 tool.\u003c/p\u003e\n \u003cp\u003eOverall, 2 of the 23 studies showed a high risk of bias and 8 others raised some concerns.\u003c/p\u003e\n \u003cp\u003eA \u0026ldquo;traffic light\u0026rdquo; summary of the \u0026ldquo;low\u0026rdquo;, \u0026ldquo;high\u0026rdquo;, or \u0026ldquo;some concerns\u0026rdquo; risk of bias assessment of the included studies via 5 domains is presented in Fig. \u003cspan class=\"InternalRef\"\u003e3\u003c/span\u003ea.\u003c/p\u003e\n \u003cp\u003eThe weighted bar plot (Fig. \u003cspan class=\"InternalRef\"\u003e3\u003c/span\u003eb) provides a graphical representation of the distribution of risk-of-bias judgments within each bias domain. Since the judgments are weighted, the segments represent the proportional distribution of studies categorized as \u0026ldquo;low,\u0026rdquo; \u0026ldquo;some concerns,\u0026rdquo; and \u0026ldquo;high.\u0026rdquo; Consequently, the overall risk-of-bias bar indicates an increase in the percentage of studies categorized as \u0026ldquo;some concerns,\u0026rdquo; reflecting the consideration of various types of biases and the relative importance of each study.\u003c/p\u003e\n \u003cp\u003eEight of the twenty tree included articles (35%) exhibited bias related to the randomization process. This finding is problematic, as randomization is essential for minimizing bias and ensuring comparability between treatment groups. The fact that in this domain 6 articles were categorized as having \u0026quot;some concerns\u0026quot; and 2 with \u0026quot;high risk of bias\u0026quot; suggests that this issue is rather significant.\u003c/p\u003e\n \u003cp\u003eSome of the articles raised concerns due to deviations from intended intervention and missing outcome data. Such deviations can significantly impact the validity of the results, as they may lead to inconsistencies in treatment application and hinder the reproducibility of findings. Missing data further complicates interpretations and could skew results, making it difficult to assess the true effects of the interventions evaluated.\u003c/p\u003e\n \u003cp\u003eAll articles except one showed a low risk of bias in selection of the reported result. With a single study displaying a risk of bias in this area, it seems to be a relative strength of the included studies. This suggests that, in most cases, researchers appear to have reported results in a transparent and unbiased manner, mitigating potential concerns of selective outcome reporting.\u003c/p\u003e\n \u003cp\u003eNone of the studies were associated with bias in measurement of the outcome, indicating that once an outcome was defined, the measurements were consistently applied across studies. This stability in measurement suggests that the outcomes reported can be trusted to reflect the intended constructs reliably, although the initial deviations in intervention could still detract from overall confidence in the findings.\u003c/p\u003e\n \u003cp\u003eThe risk of bias assessment presents a mixed landscape among the included studies. While certain aspects demonstrate robustness, significant concerns require careful consideration. The identification of two studies with a \u0026quot;high risk of bias\u0026quot; alongside the eight additional studies raising \u0026quot;some concerns\u0026quot; serves as a call to action for researchers in this field. It underscores the necessity for attentive methodology and transparent reporting in order to enhance the reliability of findings. This assessment is particularly timely as it paves the way for future research endeavors to focus on reducing these biases, ensuring that the resultant evidence is robust.\u003c/p\u003e\n \u003c/div\u003e\n\u003c/div\u003e\n\u003cdiv id=\"Sec17\" class=\"Section2\"\u003e\n \u003ch2\u003eImmunogenicity\u003c/h2\u003e\n \u003cdiv class=\"BlockQuote\"\u003e\n \u003cp\u003eOverall, the majority of the studies reported on the efficacy of different types of vaccine against the three poliovirus strains (Sabin 1\u0026ndash;3). This was confirmed by the increase of antibodies after complete immunization programs and evident from the GMR ranging from 7.1 to 1,172.7 for serotype 1, from 2.0 to 327.2 for serotype 2 and from 12.8 to 590.7 for serotype 3 (titer below 8 are considered non-protective, i.e. negative). Seroconversion rates (SR) consistently varied from 91.5 and 95.1 to 100.0 for serotypes 1 and 3 respectively; for type 2 the lowest values were 45.7, 49.0 and 66.7 (Supplementary Table\u0026nbsp;1).\u003c/p\u003e\n \u003cp\u003ePrimary immunization with 3 IPV doses showed generally high GMRs and SR rates, with sIPV groups exhibiting similar values. Likewise, fractional IPV doses (1/10) exhibited the same immunogenicity as full doses, in some IPV-Al (IM) groups demonstrating even higher values. Comparison of the GMTs in groups administered (s)IPV as opposed to OPV showed, that a single dose of nOPV2 as primary or 1\u0026ndash;2 doses as boost immunization is not enough to build immunity against PV2 (SR\u0026thinsp;=\u0026thinsp;45.7, 49.0 for primary and 66.7 for boost), however a full primary vaccination with tOPV or nOPV2 exhibits GMRs and SR against PV2 similar to (s)IPV. This indicates that all the above-mentioned vaccination schedules are interchangeable and effective.\u003c/p\u003e\n \u003cp\u003eThe peak results were recorded among schedules of sIPV with bOPV and combinations of IPV with vaccines against other diseases (DTaP, PRP etc); sIPV-sIPV-bOPV demonstrated the highest antibody levels and 100% seroconversion for serotype 1 and 3, with the GMRs being 1,172.7 and 887.6, respectively. The highest GMR value for serotype 2 was shown by the DTPa-IPV\u0026thinsp;+\u0026thinsp;Hib and is equal to 327.2 (SR also 100%). IPV\u0026thinsp;+\u0026thinsp;RV5 and DTwP-IPV-HB-PRP\u0026thinsp;~\u0026thinsp;T had one of the highest GMR scores for all three serotypes (354.6, 117.7, 540.9 and 351.2, 258.8, 573.6, respectively); Clearly sIPV and IPV that are the main vaccines in these schedules, are the reason for such results, but the fact that they were a part of a combination schedule cannot be overlooked: whether DTaP or PRP \u0026sim; T had affected IPV can only be stated after additional research on the matter. In the sIPV-sIPV-bOPV study it was probably the presence of an extra sIPV dose that led to the highest GMRs for ST 1 and 3, since sIPV-bOPV-bOPV had lower antibody rates for these serotypes.\u003c/p\u003e\n \u003cp\u003eIt is important to note that the lowest GMRs against type 2 were reported in the sIPV-bOPV-bOPV and IPV-bOPV-bOPV groups (4.6 and 2.0) and D\u003csub\u003eA\u003c/sub\u003eT\u003csub\u003eA\u003c/sub\u003ePa-HBV-IPV/Hib and D\u003csub\u003eB\u003c/sub\u003eT\u003csub\u003eB\u003c/sub\u003ePa-HBV-IPV/Hib groups with values ranging from 3.7 to 13.8 between the 3 serotypes. Both D\u003csub\u003eA\u003c/sub\u003eT\u003csub\u003eA\u003c/sub\u003ePa-HBV-IPV/Hib and D\u003csub\u003eB\u003c/sub\u003eT\u003csub\u003eB\u003c/sub\u003ePa-HBV-IPV/Hib groups belong to the same study, as does the 238 participants DTPa-HBV-IPV/ Hib group, that also has low GMR rates in comparison to groups that were administered the same vaccine but were part of other studies. Taking this into consideration, it could be possible that these particular groups are not sufficient for making any conclusions on the efficacy of the studied vaccines.\u003c/p\u003e\n \u003cp\u003eWhen it comes to the IPV-bOPV-bOPV group, seroconversion for type 2 was unusually low \u0026ndash; only 55.8%. Moreover, in IPV-IPV-bOPV group post-vaccination values were also rather low (GMT\u0026thinsp;=\u0026thinsp;8.8 and SC\u0026thinsp;=\u0026thinsp;82.6), hence it is clear that one or two doses of IPV in primary immunization is insufficient for inducing immunity to PV 2. Although the wild polio type 2 is eradicated, such low antibody levels might still pose a threat due to cVDPVs. Thus, as nOPV2 and tOPV showed very similar average GMR rates in comparison to full-dose IPV or sIPV, it is important to keep oral polio vaccine a part of the immunization \u003csup\u003e\u003cspan class=\"CitationRef\"\u003e55\u003c/span\u003e\u003c/sup\u003e.\u003c/p\u003e\n \u003c/div\u003e\n\u003c/div\u003e\n\u003cdiv id=\"Sec18\" class=\"Section2\"\u003e\n \u003ch2\u003eSafety assessment\u003c/h2\u003e\n \u003cdiv class=\"BlockQuote\"\u003e\n \u003cp\u003eAn important part of this systematic review was the assessment of the safety of vaccines. The main findings are as follows: vaccines were considered well-tolerated and safe; however, some articles mentioned the need for further research; most common adverse events (AEs) were fever (pyrexia), abnormal crying, diarrhea, vomiting, drowsiness, irritability, injection site sensitivity (tenderness)/pain/erythema, swelling; uncommon were pneumonia, upper/lower respiratory tract infections, bronchiolitis. Most frequently reported AEs were generally consistent with the typical side effects of vaccination \u003csup\u003e\u003cspan class=\"CitationRef\"\u003e56\u003c/span\u003e\u003c/sup\u003e.\u003c/p\u003e\n \u003cp\u003eUnfortunately, a comprehensive statistical comparison of AEs was not feasible due to the varying presentation of results across the publications. Some studies provided only general data on the frequency of AEs within specific groups, expressed as percentages. In contrast, other studies offered detailed summaries of individual cases of AEs occurring at different vaccination stages, categorized by specific AE types. Additionally, some articles reported data as the number of patients who developed particular AEs. This inconsistency rendered mathematical processing of the data impossible. Nevertheless, the primary trends identified through the analysis are presented below.\u003c/p\u003e\n \u003cp\u003eOverall, all individual vaccines demonstrated a satisfactory level of safety in the conducted studies. When different individual vaccine types (IPV, sIVP, or tOPV) were compared in a single study, no statistically significant differences were found between the study groups, indicating a similar safety profile.\u003c/p\u003e\n \u003cp\u003eFor different doses of IPV-Al there was either an extensive list of AEs, or a complete lack of data, hence, more research is needed to gather data on the safety of aluminum-adjuvanted polio vaccines, given that they provide a strong immune response, are widely used, and are considered to be safe \u003csup\u003e\u003cspan class=\"CitationRef\"\u003e57\u003c/span\u003e\u003c/sup\u003e.\u003c/p\u003e\n \u003cp\u003eAE data for IPV-bOPV-bOPV did not contain any differences in comparison to similar vaccination groups, the same applies to D\u003csub\u003eB\u003c/sub\u003eT\u003csub\u003eB\u003c/sub\u003ePa-HBV-IPV/Hib. The general trend for AEs of combinations was similar to single-component vaccines: injection site reactions were most frequent, systemic reactions (like fever, irritability, drowsiness, crying, loss of appetite, vomiting, diarrhea) were all common. It is important to note, that one of the fatal AE occurred in the D\u003csub\u003eA\u003c/sub\u003eT\u003csub\u003eA\u003c/sub\u003ePa -HBV-IPV/Hib (asphyxia and interstitial lung disease) study and the other one in the DTaP-IPV/Hib (infectious shock due to acute bronchopneumonia and congestive heart failure) group. These deaths were not considered as related to the vaccine.\u003c/p\u003e\n \u003cp\u003eThe analysis of AEs related to combined vaccines suggests that they tend to have higher rates of local reactions and fever compared to single-component vaccines. This outcome aligns with the main technological challenge of combined vaccines \u0026ndash; the administration of multiple antigens simultaneously. While this increases the possibility of local adverse events, multicomponent vaccines are essential to address the growing number of vaccines required for infants and children. These vaccines have the potential to become the key part of any type of immunization against a wide range of diseases \u003csup\u003e\u003cspan class=\"CitationRef\"\u003e58\u003c/span\u003e\u003c/sup\u003e.\u003c/p\u003e\n \u003cp\u003eAmong the studies, three fatal cases were recorded. The causes of death were asphyxia and interstitial lung disease for one case, septic shock for another, and infectious shock due to acute bronchopneumonia and congestive heart failure for the third. The third case occurred one day after the final vaccine dose, while the first and second occurred 17 and 30 days later, respectively. All three fatalities were considered unrelated to vaccination.\u003c/p\u003e\n \u003c/div\u003e\n\u003c/div\u003e\n\u003cdiv id=\"Sec19\" class=\"Section2\"\u003e\n \u003ch2\u003e3.7 Baseline GMTs\u003c/h2\u003e\n \u003cdiv class=\"BlockQuote\"\u003e\n \u003cp\u003eConsidering the geographical differences, the baseline (preprimary) GMTs did vary for each poliovirus type across the studies, with the pre-vaccination type 3 titers being considerably lower than type 1 and 2 titers. Highest baseline GMTs: Bangladesh (29.3 for ST1, 56.5 for ST2, 15.1 for ST3), India (31.9 and 53.5 for ST1, 36.2 and 32.5 for ST2, 11.9 for ST 3), Dominican Republic (53.7/ 47.4/ 46.4/ 51.6 for ST2, 13.0 and 12.5 for ST3). Lowest baseline GMTs: Japan (3.58 and 3.35 for ST1, 5.06 and 5.55 for ST2, 2.95/ 2.86/ 3.61 for ST3), South Korea (4.80 and 4.26 for ST1, 4.34 and 4.48 for ST3), Thailand (6.70/ 6.07/ 6.66/ 6.47 for ST 1). Out of the 23 studies 9 were conducted in China, in these articles the baseline GMTs varied from 5.55 to 21.10 for ST 1; from 5.00 to 9.76 for ST2, from 4.34 to 8.08 for ST3.\u003c/p\u003e\n \u003cp\u003eBaseline GMTs for Japan, Bangladesh and India are very abnormal when compared to other values. Although these numbers are clearly noteworthy, it is also important to consider that the analysis included only one study from each of the countries, and more data is needed to establish a correlation between baseline GMT rates and the country of the article\u0026rsquo;s origin. The samples are too insufficient, especially in comparison to nine different articles conducted in different regions of China, all of which showed very similar GMT rates for ST2 and 3.\u003c/p\u003e\n \u003cp\u003eIt is, however, important to note, that India and Bangladesh have been polio-free since 2014 \u0026ndash; later, when compared to other countries \u0026ndash; and are in direct proximity to Pakistan and Afghanistan, the only endemic regions; a high poverty rate in India is also consistent with pre-disposal to vaccine-preventable diseases. All in all, it is possible that these factors could have led to higher baseline GMT rates in these countries \u003csup\u003e\u003cspan class=\"CitationRef\"\u003e59\u003c/span\u003e\u003c/sup\u003e.\u003c/p\u003e\n \u003cp\u003eIn contrast, Japan has been polio-free since 1980, largely due to its strong healthcare system, comprehensive vaccination programs, and low exposure to the virus. Low GMTs could indicate that the immunity levels in the general population are relatively high and isolation from endemic regions has reduced the risk of polio cases \u003csup\u003e\u003cspan class=\"CitationRef\"\u003e60\u003c/span\u003e\u003c/sup\u003e.\u003c/p\u003e\n \u003c/div\u003e\n\u003c/div\u003e\n\u003cdiv id=\"Sec20\" class=\"Section2\"\u003e\n \u003ch2\u003eLimitations\u003c/h2\u003e\n \u003cdiv class=\"BlockQuote\"\u003e\n \u003cp\u003eThis analysis has some limitations that must be considered in interpreting the results. Firstly, the sample sizes in Table \u003cspan class=\"InternalRef\"\u003e1\u003c/span\u003e only included participants who fully completed the vaccination, while the AE data came from all participants who received at least one vaccine dose. There was no follow-up AE information for those who have finished the study, leading to inconsistencies between the sample sizes and AE numbers.\u003c/p\u003e\n \u003cp\u003eSecondly, the sample sizes among the 60 immunization groups varied greatly from 10 to 810, with an average number of participants of about 224. As a result, such a range of numbers complicated the comparison process of some vaccination groups, especially their AEs: In some cases, because the samples are so different, it is impossible to make a clear connection between the amount and diversity of side effects and the administered vaccine. Moreover, the articles used different methods of recording and presenting AE data, and some studies did not present that data in a way that was usable. Because of this, a proper comparison and evaluation of the AEs was not possible, which limited the quality of the analysis. Using standardized approaches among studies would help to generate higher-quality analyses.\u003c/p\u003e\n \u003cp\u003eThirdly, only studies that contained GMT data were included in the review. This resulted in a nearly 5-fold decrease in the number of eligible articles, as there are several other ways to assess the immunogenicity (e.g. geometric mean concentration, median/mean titers, and vaccine efficacy). When measuring the immunity response induced by a vaccine, GMT is most commonly used, as it allows to analyze antibody levels in large groups by giving a good representation of skewed data \u003csup\u003e\u003cspan class=\"CitationRef\"\u003e61\u003c/span\u003e\u003c/sup\u003e. That is why in this systematic review the geometric mean titers ratio was calculated from the extracted GMT data in order to analyze the immunogenicity value of various polio vaccines and find the connections or the absence of such between different studies and their findings.\u003c/p\u003e\n \u003cp\u003eIt is also important to note that children under six months may have circulating antibodies to polio transmitted from their mothers. Therefore, the higher the polio vaccination coverage in the study region, the more antibodies a child may receive at birth. This could potentially complicate the calculation of SR.\u003c/p\u003e\n \u003c/div\u003e\n\u003c/div\u003e"},{"header":"Conclusion","content":"\u003cp\u003eThe systematic review contains an analysis and comparison of the polio vaccines and provides evidence of their immunogenicity and safety. The data is structured and presented in such a way, as to provide a clear overview of all the different immunization approaches and their performances.\u003c/p\u003e\n\u003cp\u003eThe study demonstrated that both IPV and sIPV are well-suited for the primary vaccination series, which includes three doses of the vaccine against poliomyelitis. However, a single or double administration is insufficient to establish stable immunity. It is also possible to reduce the dose of the administered antigen when using IPV-Al without compromising the levels of SR and GMR. This approach could potentially decrease the incidence of AEs and enhance compliance among patients in the context of population immunization. Additionally, tOPV is well-suited for establishing primary immunity, showing SR and GMR values comparable to those of IPV and sIPV.\u003c/p\u003e\n\u003cp\u003eIn future studies on efficacy and immunogenicity against poliomyelitis, it is essential to provide a more detailed account of the incidence of AEs, which will facilitate a more comprehensive comparison of different types of vaccines.\u003c/p\u003e"},{"header":"Declarations","content":"\u003cp\u003e\u003cstrong\u003eEthics approval and consent to participate\u003c/strong\u003e\u003c/p\u003e\n\u003cp\u003eNot applicable.\u003c/p\u003e\n\u003cp\u003e\u003cstrong\u003eConsent for publication\u003c/strong\u003e\u003c/p\u003e\n\u003cp\u003eNot applicable.\u003c/p\u003e\n\u003cp\u003e\u003cstrong\u003eAvailability of data and materials\u003c/strong\u003e\u003c/p\u003e\n\u003cp\u003eAll data generated or analysed during this study are included in this published article and its supplementary information files.\u003c/p\u003e\n\u003cp\u003e\u003cstrong\u003eCompeting interests\u003c/strong\u003e\u003c/p\u003e\n\u003cp\u003eThe authors declare no conflict of interest. The funders had no role in the design of the study; in the collection, analyses, or interpretation of data; in the writing of the manuscript, or in the decision to publish the results.\u003c/p\u003e\n\u003cp\u003eFunding\u0026nbsp;\u003c/p\u003e\n\u003cp\u003eThis research was funded by Russian Science Foundation, grant number 23-15-00471.\u003c/p\u003e\n\u003cp\u003e\u003cstrong\u003eAuthors\u0026apos; contributions\u003c/strong\u003e\u003c/p\u003e\n\u003cp\u003eR.P.T. and L.I.K. conceived and designed the study. M.D.K., A.A.Kh., M.A.V., and A.N.P. conducted literature review and data processing. A.A.S. and A.T. performed data curation. R.P.T., A.A.S., and A.A.Kh. carried out statistical analyses. R.P.T. and M.D.K. performed data visualization. A.A.S., M.D.K., A.A.Kh., and L.I.K. drafted the results section. All authors contributed to data interpretation and discussion. Yu.Yu.I. and D.D.Zh. supervised manuscript preparation and provided critical revisions. D.D.Zh. acquired funding. All authors reviewed, edited, and approved the final manuscript prior to submission.\u003c/p\u003e\n\u003cp\u003e\u003cstrong\u003eAcknowledgments\u003c/strong\u003e\u003c/p\u003e\n\u003cp\u003eNot applicable.\u003c/p\u003e"},{"header":"References","content":"\u003col\u003e\n \u003cli\u003eHogle, J. M., Chow, M. \u0026amp; Filman, D. J. Three-Dimensional Structure of Poliovirus at 2.9 \u0026Aring; Resolution. \u003cem\u003eScience\u003c/em\u003e \u003cstrong\u003e229\u003c/strong\u003e, 1358\u0026ndash;1365 (1985).\u003c/li\u003e\n \u003cli\u003eBurrill, C. P. \u003cem\u003eet al.\u003c/em\u003e Global RNA Structure Analysis of Poliovirus Identifies a Conserved RNA Structure Involved in Viral Replication and Infectivity. \u003cem\u003eJ. Virol.\u003c/em\u003e (2013) doi:10.1128/jvi.01560-13.\u003c/li\u003e\n \u003cli\u003eMehndiratta, M. M., Mehndiratta, P. \u0026amp; Pande, R. Poliomyelitis: Historical Facts, Epidemiology, and Current Challenges in Eradication. \u003cem\u003eThe Neurohospitalist\u003c/em\u003e \u003cstrong\u003e4\u003c/strong\u003e, 223\u0026ndash;229 (2014).\u003c/li\u003e\n \u003cli\u003e\u003cem\u003eSherris Medical Microbiology: An Introduction to Infectious Diseases\u003c/em\u003e. (McGraw-Hill, New York, 2004).\u003c/li\u003e\n \u003cli\u003ePoliomyelitis (polio). https://www.who.int/health-topics/poliomyelitis.\u003c/li\u003e\n \u003cli\u003eGPEI-Wild Poliovirus. https://polioeradication.org/wild-poliovirus/.\u003c/li\u003e\n \u003cli\u003eGPEI-The Vaccines. https://polioeradication.org/about-polio/the-vaccines/.\u003c/li\u003e\n \u003cli\u003eGPEI-Polio this week. https://polioeradication.org/about-polio/polio-this-week/.\u003c/li\u003e\n \u003cli\u003eZaffran, M., McGovern, M., Hossaini, R., Martin, R. \u0026amp; Wenger, J. The polio endgame: securing a world free of all polioviruses. \u003cem\u003eThe Lancet\u003c/em\u003e \u003cstrong\u003e391\u003c/strong\u003e, 11\u0026ndash;13 (2018).\u003c/li\u003e\n \u003cli\u003eGPEI-Variant Poliovirus (cVDPV). https://polioeradication.org/about-polio/the-virus/vaccine-derived-polioviruses/.\u003c/li\u003e\n \u003cli\u003eMinor, P. Vaccine-derived poliovirus (VDPV): Impact on poliomyelitis eradication. \u003cem\u003eVaccine\u003c/em\u003e \u003cstrong\u003e27\u003c/strong\u003e, 2649\u0026ndash;2652 (2009).\u003c/li\u003e\n \u003cli\u003eKew, O. M., Sutter, R. W., Gourville, E. M. de, Dowdle, W. R. \u0026amp; Pallansch, M. A. VACCINE-DERIVED POLIOVIRUSES AND THE ENDGAME STRATEGY FOR GLOBAL POLIO ERADICATION*. \u003cem\u003eAnnu. Rev. Microbiol.\u003c/em\u003e \u003cstrong\u003e59\u003c/strong\u003e, 587\u0026ndash;635 (2005).\u003c/li\u003e\n \u003cli\u003ePatel, M., Zipursky, S., Orenstein, W., Garon, J. \u0026amp; Zaffran, M. Polio endgame: the global introduction of inactivated polio vaccine. \u003cem\u003eExpert Rev. Vaccines\u003c/em\u003e \u003cstrong\u003e14\u003c/strong\u003e, 749\u0026ndash;762 (2015).\u003c/li\u003e\n \u003cli\u003eSutter, R. W. \u003cem\u003eet al.\u003c/em\u003e Immunogenicity of a new routine vaccination schedule for global poliomyelitis prevention: an open-label, randomised controlled trial. \u003cem\u003eThe Lancet\u003c/em\u003e \u003cstrong\u003e386\u003c/strong\u003e, 2413\u0026ndash;2421 (2015).\u003c/li\u003e\n \u003cli\u003eAsturias, E. J. \u003cem\u003eet al.\u003c/em\u003e Humoral and intestinal immunity induced by new schedules of bivalent oral poliovirus vaccine and one or two doses of inactivated poliovirus vaccine in Latin American infants: an open-label randomised controlled trial. \u003cem\u003eThe Lancet\u003c/em\u003e \u003cstrong\u003e388\u003c/strong\u003e, 158\u0026ndash;169 (2016).\u003c/li\u003e\n \u003cli\u003eModlin, J. F. \u0026amp; Chumakov, K. Sabin Strain Inactivated Polio Vaccine for the Polio Endgame. \u003cem\u003eJ. Infect. Dis.\u003c/em\u003e \u003cstrong\u003e221\u003c/strong\u003e, 504\u0026ndash;505 (2020).\u003c/li\u003e\n \u003cli\u003eHampton, L. M. Cessation of Trivalent Oral Poliovirus Vaccine and Introduction of Inactivated Poliovirus Vaccine \u0026mdash; Worldwide, 2016. \u003cem\u003eMMWR Morb. Mortal. Wkly. Rep.\u003c/em\u003e \u003cstrong\u003e65\u003c/strong\u003e, (2016).\u003c/li\u003e\n \u003cli\u003eKhan, M. M. \u0026amp; Ehreth, J. Costs and benefits of polio eradication: a long-run global perspective. \u003cem\u003eVaccine\u003c/em\u003e \u003cstrong\u003e21\u003c/strong\u003e, 702\u0026ndash;705 (2003).\u003c/li\u003e\n \u003cli\u003eDuintjer Tebbens, R. J. \u003cem\u003eet al.\u003c/em\u003e Economic analysis of the global polio eradication initiative. \u003cem\u003eVaccine\u003c/em\u003e \u003cstrong\u003e29\u003c/strong\u003e, 334\u0026ndash;343 (2010).\u003c/li\u003e\n \u003cli\u003eGPEI-Vaccine Derived Poliovirus count. https://polioeradication.org/circulating-vaccine-derived-poliovirus-count/.\u003c/li\u003e\n \u003cli\u003ePolio eradication strategy 2022\u0026ndash;2026: delivering on a promise. https://www.who.int/publications/i/item/9789240031937.\u003c/li\u003e\n \u003cli\u003eThe PRISMA 2020 statement: an updated guideline for reporting systematic reviews | The BMJ. https://doi.org/10.1136/bmj.n71.\u003c/li\u003e\n \u003cli\u003ePROSPERO: An International Register of Systematic Review Protocols: Medical Reference Services Quarterly: Vol 38 , No 2 - Get Access. https://www.tandfonline.com/doi/full/10.1080/02763869.2019.1588072.\u003c/li\u003e\n \u003cli\u003eCochrane Handbook for Systematic Reviews of Interventions | Wiley Online Books. https://onlinelibrary.wiley.com/doi/book/10.1002/9780470712184.\u003c/li\u003e\n \u003cli\u003eRoB 2: a revised tool for assessing risk of bias in randomised trials | The BMJ. https://www.bmj.com/content/366/bmj.l4898.\u003c/li\u003e\n \u003cli\u003eMcGuinness, L. A. \u0026amp; Higgins, J. P. T. Risk‐of‐bias VISualization (robvis): An R package and Shiny web app for visualizing risk‐of‐bias assessments. \u003cem\u003eRes. Synth. Methods\u003c/em\u003e \u003cstrong\u003e12\u003c/strong\u003e, 55\u0026ndash;61 (2021).\u003c/li\u003e\n \u003cli\u003eThelwall, M. \u0026amp; Sud, P. Scopus 1900\u0026ndash;2020: Growth in articles, abstracts, countries, fields, and journals. \u003cem\u003eQuant. Sci. Stud.\u003c/em\u003e \u003cstrong\u003e3\u003c/strong\u003e, 37\u0026ndash;50 (2022).\u003c/li\u003e\n \u003cli\u003eGPEI-History of Polio. https://polioeradication.org/about-polio/history-of-polio/.\u003c/li\u003e\n \u003cli\u003evan Eck, N. J. \u0026amp; Waltman, L. Software survey: VOSviewer, a computer program for bibliometric mapping. \u003cem\u003eScientometrics\u003c/em\u003e \u003cstrong\u003e84\u003c/strong\u003e, 523\u0026ndash;538 (2010).\u003c/li\u003e\n \u003cli\u003eEck, N. J. van \u0026amp; Waltman, L. Text mining and visualization using VOSviewer. Preprint at https://doi.org/10.48550/arXiv.1109.2058 (2011).\u003c/li\u003e\n \u003cli\u003eA smart local moving algorithm for large-scale modularity-based community detection | The European Physical Journal B. https://link.springer.com/article/10.1140/epjb/e2013-40829-0#citeas.\u003c/li\u003e\n \u003cli\u003eRivera, L. \u003cem\u003eet al.\u003c/em\u003e Immunogenicity and safety of three aluminium hydroxide adjuvanted vaccines with reduced doses of inactivated polio vaccine (IPV-Al) compared with standard IPV in young infants in the Dominican Republic: a phase 2, non-inferiority, observer-blinded, randomised, and controlled dose investigation trial. \u003cem\u003eLancet Infect. Dis.\u003c/em\u003e \u003cstrong\u003e17\u003c/strong\u003e, 745\u0026ndash;753 (2017).\u003c/li\u003e\n \u003cli\u003eFeng, G. \u003cem\u003eet al.\u003c/em\u003e Safety, immunogenicity, and lot-to-lot consistency of a multidose Sabin strain-based inactivated polio vaccine: a phase III, randomized, blinded, positive-control clinical trial in infants aged 2 months. \u003cem\u003eInt. J. Infect. Dis.\u003c/em\u003e \u003cstrong\u003e130\u003c/strong\u003e, 20\u0026ndash;27 (2023).\u003c/li\u003e\n \u003cli\u003eLi, R. \u003cem\u003eet al.\u003c/em\u003e Primary and booster vaccination with an inactivated poliovirus vaccine (IPV) is immunogenic and well-tolerated in infants and toddlers in China. \u003cem\u003eVaccine\u003c/em\u003e \u003cstrong\u003e34\u003c/strong\u003e, 1436\u0026ndash;1443 (2016).\u003c/li\u003e\n \u003cli\u003eQiu, J. \u003cem\u003eet al.\u003c/em\u003e Immunogenicity and safety evaluation of bivalent types 1 and 3 oral poliovirus vaccine by comparing different poliomyelitis vaccination schedules in China: A randomized controlled non-inferiority clinical trial. \u003cem\u003eHum. Vaccines Immunother.\u003c/em\u003e \u003cstrong\u003e13\u003c/strong\u003e, 1359\u0026ndash;1368 (2017).\u003c/li\u003e\n \u003cli\u003eCapeding, M. R. \u003cem\u003eet al.\u003c/em\u003e Safety and Immunogenicity of a New Inactivated Polio Vaccine Made From Sabin Strains: A Randomized, Double-Blind, Active-Controlled, Phase 2/3 Seamless Study. \u003cem\u003eJ. Infect. Dis.\u003c/em\u003e \u003cstrong\u003e226\u003c/strong\u003e, 308\u0026ndash;318 (2022).\u003c/li\u003e\n \u003cli\u003eS\u0026aacute;ez-Llorens, X. \u003cem\u003eet al.\u003c/em\u003e Immunogenicity and safety of an adjuvanted inactivated polio vaccine, IPV-Al, following vaccination in children at 2, 4, 6 and at 15\u0026ndash;18 months. \u003cem\u003eVaccine\u003c/em\u003e \u003cstrong\u003e38\u003c/strong\u003e, 3780\u0026ndash;3789 (2020).\u003c/li\u003e\n \u003cli\u003eYan, S. \u003cem\u003eet al.\u003c/em\u003e Immunogenicity and safety of different sequential schedules of Sabin strain-based inactivated poliovirus vaccination: A randomized, controlled, open-label, phase IV clinical trial in China. \u003cem\u003eVaccine\u003c/em\u003e \u003cstrong\u003e38\u003c/strong\u003e, 6274\u0026ndash;6279 (2020).\u003c/li\u003e\n \u003cli\u003eJiang, R. \u003cem\u003eet al.\u003c/em\u003e Immunogenicity and safety of the inactivated poliomyelitis vaccine made from Sabin strains in a phase IV clinical trial for the vaccination of a large population. \u003cem\u003eVaccine\u003c/em\u003e \u003cstrong\u003e39\u003c/strong\u003e, 1463\u0026ndash;1471 (2021).\u003c/li\u003e\n \u003cli\u003eSun, X. \u003cem\u003eet al.\u003c/em\u003e Immunogenicity and safety of concomitant administration of the chinese inactivated poliovirus vaccine with the diphtheria-tetanus-acellular pertussis (DTaP) vaccine in children: A multicenter, randomized, non-inferiority, controlled trial. \u003cem\u003eFront. Immunol.\u003c/em\u003e \u003cstrong\u003e13\u003c/strong\u003e, 905634 (2022).\u003c/li\u003e\n \u003cli\u003eZaman, K. \u003cem\u003eet al.\u003c/em\u003e Evaluation of the safety, immunogenicity, and faecal shedding of novel oral polio vaccine type 2 in healthy newborn infants in Bangladesh: a randomised, controlled, phase 2 clinical trial. \u003cem\u003eThe Lancet\u003c/em\u003e \u003cstrong\u003e401\u003c/strong\u003e, 131\u0026ndash;139 (2023).\u003c/li\u003e\n \u003cli\u003eOchoge, M. \u003cem\u003eet al.\u003c/em\u003e Safety of the novel oral poliovirus vaccine type 2 (nOPV2) in infants and young children aged 1 to \u0026lt;5 years and lot-to-lot consistency of the immune response to nOPV2 in infants in The Gambia: a phase 3, double-blind, randomised controlled trial. \u003cem\u003eThe Lancet\u003c/em\u003e \u003cstrong\u003e403\u003c/strong\u003e, 1164\u0026ndash;1175 (2024).\u003c/li\u003e\n \u003cli\u003eRivera Mej\u0026iacute;a, L. \u003cem\u003eet al.\u003c/em\u003e Safety and immunogenicity of shorter interval schedules of the novel oral poliovirus vaccine type 2 in infants: a phase 3, randomised, controlled, non-inferiority study in the Dominican Republic. \u003cem\u003eLancet Infect. Dis.\u003c/em\u003e \u003cstrong\u003e24\u003c/strong\u003e, 275\u0026ndash;284 (2024).\u003c/li\u003e\n \u003cli\u003eTang, R. \u003cem\u003eet al.\u003c/em\u003e A phase Ⅱ, randomized, controlled trial to evaluate the safety and immunogenicity of a Sabin strain-based inactivated polio vaccine. \u003cem\u003eHum. Vaccines Immunother.\u003c/em\u003e \u003cstrong\u003e16\u003c/strong\u003e, 2641\u0026ndash;2648 (2020).\u003c/li\u003e\n \u003cli\u003eCadorna-Carlos, J., Vidor, E. \u0026amp; Bonnet, M.-C. Randomized controlled study of fractional doses of inactivated poliovirus vaccine administered intradermally with a needle in the Philippines. \u003cem\u003eInt. J. Infect. Dis.\u003c/em\u003e \u003cstrong\u003e16\u003c/strong\u003e, e110\u0026ndash;e116 (2012).\u003c/li\u003e\n \u003cli\u003eSanchez, L. \u003cem\u003eet al.\u003c/em\u003e Immunogenicity and Safety of a Hexavalent DTwP-IPV-HB-PRP~T Vaccine Versus Separate DTwP-HB-PRP~T, bOPV, and IPV Vaccines Administered at 2, 4, 6 Months of Age Concomitantly With Rotavirus and Pneumococcal Conjugate Vaccines in Healthy Infants in Thailand. \u003cem\u003ePediatr. Infect. Dis. J.\u003c/em\u003e \u003cstrong\u003e42\u003c/strong\u003e, 711\u0026ndash;718 (2023).\u003c/li\u003e\n \u003cli\u003eNakayama, T. \u003cem\u003eet al.\u003c/em\u003e Immunogenicity and safety of a DTaP-IPV/Hib pentavalent vaccine given as primary and booster vaccinations in healthy infants and toddlers in Japan. \u003cem\u003eJ. Infect. Chemother.\u003c/em\u003e \u003cstrong\u003e26\u003c/strong\u003e, 651\u0026ndash;659 (2020).\u003c/li\u003e\n \u003cli\u003eLi, Y. \u003cem\u003eet al.\u003c/em\u003e Safety, immunogenicity and persistence of immune response to the combined diphtheria, tetanus, acellular pertussis, poliovirus and \u003cem\u003eHaemophilus influenzae\u003c/em\u003e type b conjugate vaccine (DTPa-IPV/Hib) administered in Chinese infants. \u003cem\u003eHum. Vaccines Immunother.\u003c/em\u003e \u003cstrong\u003e13\u003c/strong\u003e, 588\u0026ndash;598 (2017).\u003c/li\u003e\n \u003cli\u003eKang, J. H. \u003cem\u003eet al.\u003c/em\u003e The Immunogenicity and Safety of a Combined DTaP-IPV//Hib Vaccine Compared with Individual DTaP-IPV and Hib (PRP~T) Vaccines: a Randomized Clinical Trial in South Korean Infants. \u003cem\u003eJ. Korean Med. Sci.\u003c/em\u003e \u003cstrong\u003e31\u003c/strong\u003e, 1383 (2016).\u003c/li\u003e\n \u003cli\u003eLin, T. Y. \u003cem\u003eet al.\u003c/em\u003e A fully liquid diphtheria\u0026ndash;tetanus\u0026ndash;five component acellular pertussis\u0026ndash;inactivated poliomyelitis\u0026ndash;Haemophilus influenzae type b conjugate vaccine: immunogenicity and safety of primary vaccination in Taiwanese infants. \u003cem\u003eInt. J. Infect. Dis.\u003c/em\u003e \u003cstrong\u003e11\u003c/strong\u003e, 129\u0026ndash;136 (2007).\u003c/li\u003e\n \u003cli\u003eLim, F. S., Han, H.-H., Jacquet, J.-M. \u0026amp; Bock, H. L. Primary vaccination of infants against hepatitis B can be completed using a combined hexavalent diphtheria-tetanus-acellular pertussis-hepatitis B-inactivated poliomyelitis-Haemophilus influenzae type B vaccine. \u003cem\u003eAnn. Acad. Med. Singapore\u003c/em\u003e \u003cstrong\u003e36\u003c/strong\u003e, 801\u0026ndash;806 (2007).\u003c/li\u003e\n \u003cli\u003eLalwani, S. K. \u003cem\u003eet al.\u003c/em\u003e Immunogenicity and safety of 3-dose primary vaccination with combined DTPa-HBV-IPV/Hib in Indian infants. \u003cem\u003eHum. Vaccines Immunother.\u003c/em\u003e \u003cstrong\u003e13\u003c/strong\u003e, 120\u0026ndash;127 (2017).\u003c/li\u003e\n \u003cli\u003eVesikari, T. \u003cem\u003eet al.\u003c/em\u003e Immunogenicity and safety of primary and booster vaccination with 2 investigational formulations of diphtheria, tetanus and \u003cem\u003eHaemophilus influenzae\u003c/em\u003e type b antigens in a hexavalent DTPa-HBV-IPV/Hib combination vaccine in comparison with the licensed \u003cem\u003eInfanrix hexa\u003c/em\u003e. \u003cem\u003eHum. Vaccines Immunother.\u003c/em\u003e \u003cstrong\u003e13\u003c/strong\u003e, 1505\u0026ndash;1515 (2017).\u003c/li\u003e\n \u003cli\u003eChen, S. \u003cem\u003eet al.\u003c/em\u003e A phase 3 randomized, open-label study evaluating the immunogenicity and safety of concomitant and staggered administration of a live, pentavalent rotavirus vaccine and an inactivated poliomyelitis vaccine in healthy infants in China. \u003cem\u003eHum. Vaccines Immunother.\u003c/em\u003e \u003cstrong\u003e20\u003c/strong\u003e, 2324538 (2024).\u003c/li\u003e\n \u003cli\u003eVoorman, A. \u003cem\u003eet al.\u003c/em\u003e Analysis of population immunity to poliovirus following cessation of trivalent oral polio vaccine. \u003cem\u003eVaccine\u003c/em\u003e \u003cstrong\u003e41 Suppl 1\u003c/strong\u003e, A85\u0026ndash;A92 (2023).\u003c/li\u003e\n \u003cli\u003eIqbal, S. \u003cem\u003eet al.\u003c/em\u003e Preparation for global introduction of inactivated poliovirus vaccine: safety evidence from the US Vaccine Adverse Event Reporting System, 2000\u0026ndash;12. \u003cem\u003eLancet Infect. Dis.\u003c/em\u003e \u003cstrong\u003e15\u003c/strong\u003e, 1175\u0026ndash;1182 (2015).\u003c/li\u003e\n \u003cli\u003eHogenesch, H. Mechanism of immunopotentiation and safety of aluminum adjuvants. \u003cem\u003eFront. Immunol.\u003c/em\u003e \u003cstrong\u003e3\u003c/strong\u003e, 406 (2012).\u003c/li\u003e\n \u003cli\u003eSkibinski, D. A., Baudner, B. C., Singh, M. \u0026amp; O\u0026rsquo;Hagan, D. T. Combination Vaccines. \u003cem\u003eJ. Glob. Infect. Dis.\u003c/em\u003e \u003cstrong\u003e3\u003c/strong\u003e, 63 (2011).\u003c/li\u003e\n \u003cli\u003eJl, M. Inequity in childhood immunization in India: a systematic review. \u003cem\u003eIndian Pediatr.\u003c/em\u003e \u003cstrong\u003e49\u003c/strong\u003e, (2012).\u003c/li\u003e\n \u003cli\u003eToizumi, M., Takamatsu, M., Toda, K. \u0026amp; Horikoshi, Y. Progresses Toward Polio Eradication in Asian Countries: Its History and Japan\u0026rsquo;s Contributions. \u003cem\u003ePediatr. Infect. Dis. J.\u003c/em\u003e \u003cstrong\u003e43\u003c/strong\u003e, e347\u0026ndash;e353 (2024).\u003c/li\u003e\n \u003cli\u003eReverberi, R. The statistical analysis of immunohaematological data. \u003cem\u003eBlood Transfus.\u003c/em\u003e \u003cstrong\u003e6\u003c/strong\u003e, 37\u0026ndash;45 (2008).\u003c/li\u003e\n\u003c/ol\u003e"}],"fulltextSource":"","fullText":"","funders":[],"hasAdminPriorityOnWorkflow":false,"hasManuscriptDocX":true,"hasOptedInToPreprint":true,"hasPassedJournalQc":"","hasAnyPriority":false,"hideJournal":false,"highlight":"","institution":"","isAcceptedByJournal":true,"isAuthorSuppliedPdf":false,"isDeskRejected":"","isHiddenFromSearch":false,"isInQc":false,"isInWorkflow":false,"isPdf":false,"isPdfUpToDate":true,"isWithdrawnOrRetracted":false,"journal":{"display":true,"email":"[email protected]","identity":"virology-journal","isNatureJournal":false,"hasQc":true,"allowDirectSubmit":false,"externalIdentity":"virj","sideBox":"Learn more about [Virology Journal](http://virologyj.biomedcentral.com/)","snPcode":"12985","submissionUrl":"https://submission.nature.com/new-submission/12985/3","title":"Virology Journal","twitterHandle":"@VirologyJ","acdcEnabled":true,"dfaEnabled":true,"editorialSystem":"em","reportingPortfolio":"BMC/SO AJ","inReviewEnabled":true,"inReviewRevisionsEnabled":true},"keywords":"Poliomyelitis, Vaccines, Immunization, Immunogenicity, Infants, Systematic Review, Randomized Clinical Trials","lastPublishedDoi":"10.21203/rs.3.rs-6913898/v1","lastPublishedDoiUrl":"https://doi.org/10.21203/rs.3.rs-6913898/v1","license":{"name":"CC BY 4.0","url":"https://creativecommons.org/licenses/by/4.0/"},"manuscriptAbstract":"\u003cp\u003ePoliomyelitis, preventable only through vaccination, remains a global health concern, with wild poliovirus transmission and the emergence of vaccine-derived polioviruses. The risk of further deterioration of the situation jeopardizes efforts to eradicate polio, which has been a long-term goal for the whole world.\u003c/p\u003e \u003cp\u003e In this systematic review an analysis of randomized clinical trials was carried out to comprehensively assess the immunogenicity and safety of various polio immunization methods in infants. Geometric mean neutralizing antibody titers (GMT) data collected after 28\u0026ndash;31 days after immunization were used to calculate the geometric mean titers ratio (GMR), the analysis of which showed that both inactivated polio vaccine (IPV) and Sabin strain-based inactivated polio vaccine (sIPV) as primary vaccination induce high antibody rates, with fractional IPV showing similar results. Novel oral polio vaccine type 2 and trivalent oral polio vaccine (tOPV) also demonstrated immunogenicity in establishing immunity comparable to inactivated vaccine. High antibody levels were also induced by combined vaccine schedules, with sIPV-sIPV-bOPV and IPV combinations with diphtheria-tetanus-acellular and \u003cem\u003eHaemophilus influenzae\u003c/em\u003e type b or pentavalent rotavirus vaccine establishing particularly high antibody levels.\u003c/p\u003e \u003cp\u003eAnalysis of adverse events presented all vaccines to be well-tolerated and safe, with a tendency of combination vaccines having higher frequency of local reactions and fever.\u003c/p\u003e \u003cp\u003e While the studies presented a various landscape with some existing areas of concern, this review provides structured evidence supporting the safety and immunogenicity of existing polio vaccines, as well as highlighting the interchangeability of different vaccination approaches in infants. Future research should aim to provide detailed reporting of adverse events in order to facilitate more comprehensive assessment of vaccine efficacy.\u003c/p\u003e","manuscriptTitle":"Immunogenicity and Safety of Polio Vaccines in Infants: A Systematic Review of Randomized Clinical Trials","msid":"","msnumber":"","nonDraftVersions":[{"code":1,"date":"2025-07-01 10:45:35","doi":"10.21203/rs.3.rs-6913898/v1","editorialEvents":[{"type":"communityComments","content":0},{"type":"decision","content":"Revision requested","date":"2025-08-22T15:44:46+00:00","index":"","fulltext":""},{"type":"editorInvitedReview","content":"","date":"2025-08-22T15:37:23+00:00","index":"hide","fulltext":""},{"type":"editorInvitedReview","content":"","date":"2025-08-16T07:38:46+00:00","index":"hide","fulltext":""},{"type":"editorInvitedReview","content":"","date":"2025-08-07T18:18:01+00:00","index":"hide","fulltext":""},{"type":"reviewerAgreed","content":"90063846259180221031367199606903809353","date":"2025-08-07T15:15:00+00:00","index":"hide","fulltext":""},{"type":"reviewerAgreed","content":"53252857996552819872116184336554094462","date":"2025-08-05T14:40:08+00:00","index":"hide","fulltext":""},{"type":"reviewerAgreed","content":"314314504296114308946465115892729039299","date":"2025-08-05T14:38:19+00:00","index":"hide","fulltext":""},{"type":"editorInvitedReview","content":"","date":"2025-07-18T05:32:35+00:00","index":"hide","fulltext":""},{"type":"reviewerAgreed","content":"95341819807288696994200745527537063401","date":"2025-06-25T17:32:03+00:00","index":"hide","fulltext":""},{"type":"reviewersInvited","content":"","date":"2025-06-25T16:40:46+00:00","index":"","fulltext":""},{"type":"editorAssigned","content":"","date":"2025-06-20T14:46:24+00:00","index":"","fulltext":""},{"type":"checksComplete","content":"","date":"2025-06-20T13:41:49+00:00","index":"","fulltext":""},{"type":"submitted","content":"Virology Journal","date":"2025-06-17T11:23:31+00:00","index":"","fulltext":""}],"status":"published","journal":{"display":true,"email":"[email protected]","identity":"virology-journal","isNatureJournal":false,"hasQc":true,"allowDirectSubmit":false,"externalIdentity":"virj","sideBox":"Learn more about [Virology Journal](http://virologyj.biomedcentral.com/)","snPcode":"12985","submissionUrl":"https://submission.nature.com/new-submission/12985/3","title":"Virology Journal","twitterHandle":"@VirologyJ","acdcEnabled":true,"dfaEnabled":true,"editorialSystem":"em","reportingPortfolio":"BMC/SO AJ","inReviewEnabled":true,"inReviewRevisionsEnabled":true}}],"origin":"","ownerIdentity":"9608c99c-23fb-4be2-bf98-4cf2b3cea5a9","owner":[],"postedDate":"July 1st, 2025","published":true,"recentEditorialEvents":[],"rejectedJournal":[],"revision":"","amendment":"","status":"published-in-journal","subjectAreas":[],"tags":[],"updatedAt":"2025-11-03T16:04:57+00:00","versionOfRecord":{"articleIdentity":"rs-6913898","link":"https://doi.org/10.1186/s12985-025-02977-3","journal":{"identity":"virology-journal","isVorOnly":false,"title":"Virology Journal"},"publishedOn":"2025-10-29 15:58:04","publishedOnDateReadable":"October 29th, 2025"},"versionCreatedAt":"2025-07-01 10:45:35","video":"","vorDoi":"10.1186/s12985-025-02977-3","vorDoiUrl":"https://doi.org/10.1186/s12985-025-02977-3","workflowStages":[]},"version":"v1","identity":"rs-6913898","journalConfig":"researchsquare"},"__N_SSP":true},"page":"/article/[identity]/[[...version]]","query":{"redirect":"/article/rs-6913898","identity":"rs-6913898","version":["v1"]},"buildId":"8U1c8b4HqxoKbykW_rLl7","isFallback":false,"isExperimentalCompile":false,"dynamicIds":[84888],"gssp":true,"scriptLoader":[]}