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This paper reviews and integrates prior findings on COVID-19 mRNA vaccine platforms, focusing on the inherent adjuvanticity of mRNA–lipid nanoparticle (LNP) formulations and how this may lead to non-specific immune activation. It argues that antigen processing and immune activation pathways described in earlier work can remain unaccounted for and may contribute to immune responses toward off-target (including self) antigens, potentially affecting both immunogenic versus tolerogenic outcomes. A stated limitation is that the discussion is framed as theoretical and logical reconciliation of gaps across studies and preprints rather than a new experimental dataset. The paper does not explicitly discuss endometriosis or adenomyosis; it was included in the corpus via a keyword match in the upstream search index.
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Evidence for non-specificity of immune responses via the inherent adjuvanticity of the mRNA injections | Authorea try { document.documentElement.classList.add('js'); } catch (e) { } var _gaq = _gaq || []; _gaq.push(['_setAccount', 'G-8VDV14Y67G']); _gaq.push(['_trackPageview']); (function() { var ga = document.createElement('script'); ga.type = 'text/javascript'; ga.async = true; ga.src = ('https:' == document.location.protocol ? 'https://ssl' : 'http://www') + '.google-analytics.com/ga.js'; var s = document.getElementsByTagName('script')[0]; s.parentNode.insertBefore(ga, s); })(); Skip to main content Preprints Collections Wiley Open Research IET Open Research Ecological Society of Japan All Collections About About Authorea FAQs Contact Us Quick Search anywhere Search for preprint articles, keywords, etc. Search Search ADVANCED SEARCH SCROLL This is a preprint and has not been peer reviewed. Data may be preliminary. 11 June 2025 V1 Latest version Share on Evidence for non-specificity of immune responses via the inherent adjuvanticity of the mRNA injections Author : Siguna Mueller 0000-0002-2016-5027 [email protected] Authors Info & Affiliations https://doi.org/10.22541/au.174965573.30001463/v1 298 views 235 downloads Contents Abstract Supplementary Material Information & Authors Metrics & Citations View Options References Figures Tables Media Share Abstract One of the many novel features of the COVID-19 mRNA injections is their inherent self-adjuvanticity. It is believed that the adjuvant activity of the lipid nanoparticles (LNPs) containing ionizable or cationic lipids can explain their superiority in the induction of adaptive immune responses. Several studies have provided evidence of various immunostimulatory effects via the mRNA-LNP complexes or their individual compounds. Specifically, a 2023 study in Nature Communications implicated the mRNA compounds acting as adjuvants for the cellular immunity of mRNA technologies. In addition, this study found these injections trigger some unexpected antigen processing pathways which remained unaccounted for by the authors. A recent rational analysis of these unexpected processes identified a significant potential for adverse implications with clinical and environmental ramifications. These concerns have not been described elsewhere. Very recently, a Nature Communication study revealed some results that are difficult to align with the modus operandi of these platforms and their inherent adjuvanticity. Several logical arguments are provided to identify the nature of these gaps and how they can be explained by the unaccounted immune activation processes identified earlier. In all, this study extends the previous theoretical considerations related to several underappreciated findings about the modus operandi of mRNA technologies and seamlessly aligns existing gaps and apparently paradoxical data from recent studies. Poorly understood aspects of antigen processing and adjuvanticity converge to cause unaccounted immune responses towards targeted and off-target (self)antigens and challenge specificity and type (immunogenic vs. tolerogenic) of mRNA vaccine immunity. Supplementary Material File (evidence for non-specificity june 8.pdf) Download 516.57 KB Information & Authors Information Version history V1 Version 1 11 June 2025 Copyright This work is licensed under a Creative Commons Attribution 4.0 International License Keywords adjuvants antigen localization antigen processing and presentation cellular immunity immunogenicity mrna vaccines off-target immune effects specificity Authors Affiliations Siguna Mueller 0000-0002-2016-5027 [email protected] Center for Research in Medical Pharmacology, University of Insubria View all articles by this author Metrics & Citations Metrics Article Usage 298 views 235 downloads .FvxKWukQNSOunydq8rnd { width: 100px; } Citations Download citation Siguna Mueller. Evidence for non-specificity of immune responses via the inherent adjuvanticity of the mRNA injections. Authorea . 11 June 2025. DOI: https://doi.org/10.22541/au.174965573.30001463/v1 If you have the appropriate software installed, you can download article citation data to the citation manager of your choice. Simply select your manager software from the list below and click Download. For more information or tips please see 'Downloading to a citation manager' in the Help menu . Format Please select one from the list RIS (ProCite, Reference Manager) EndNote BibTex Medlars RefWorks Direct import Tips for downloading citations document.getElementById('citMgrHelpLink').addEventListener('click', function() { popupHelp(this.href); return false; }); $(".js__slcInclude").on("change", function(e){ if ($(this).val() == 'refworks') $('#direct').prop("checked", false); $('#direct').prop("disabled", ($(this).val() == 'refworks')); }); View Options View options PDF View PDF Figures Tables Media Share Share Share article link Copy Link Copied! Copying failed. 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