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bioRxiv · 10.1101/2025.09.09.675153

Self-multimerization of mRNA LNP-derived antigen improves antibody responses

Despins, C. A.·Round, J.·Dreolini, L.·Brown, S. D.·Holt, R.
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Abstract

BackgroundmRNA LNP technology is now being widely applied as a highly effective vaccine platform. Antigen multimerization is a well-established approach to enhance antibody titers and protective efficacy of several protein subunit vaccines. However, this approach has been less explored for mRNA LNP vaccines. MethodsHere, within the context of mRNA LNP vaccination, we used mStrawberry (mSb) as a model antigen to conduct a comprehensive, head-to-head comparison of the ability of the foldon (3-mer), IMX313 (7-mer), and ferritin (24-mer) multimerization domains to enhance immunogenicity in mice. ResultsWe compared multimerized antigen to monomeric secreted antigen and monomeric surface-displayed antigen and observed that the IMX313 domain efficiently multimerized mSb protein and enhanced anti-mSb antibody titers to a degree greater than surface-display, whereas the foldon and ferritin domains failed to multimerize or improve antibody levels. ConclusionsOur results extend the observation of enhanced immunogenicity from antigen multimerization to mRNA LNP vaccines and indicate the 7-mer forming IMX313 multimerization domain may be an ideal candidate for multimer formation in the context of mRNA LNP vaccination.

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Despins, C. A., Round, J., Dreolini, L., Brown, S. D., Holt, R.. 2025-09-15. Self-multimerization of mRNA LNP-derived antigen improves antibody responses. https://doi.org/10.1101/2025.09.09.675153

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