# Self-Multimerization of mRNA LNP-Derived Antigen Improves Antibody Responses

## TL;DR

This study shows that multimerizing an antigen using the IMX313 domain in mRNA LNP vaccines boosts antibody responses more effectively than other methods.

## Contribution

The study identifies IMX313 as a superior multimerization domain for enhancing mRNA LNP vaccine immunogenicity.

## Key findings

- The IMX313 domain efficiently multimerized mSb and significantly increased anti-mSb antibody titers.
- Foldon and ferritin domains failed to multimerize or improve antibody levels.
- Antigen multimerization improves immunogenicity in the context of mRNA LNP vaccines.

## Abstract

Background: mRNA LNP technology is now being widely applied as a highly effective vaccine platform. Antigen multimerization is a well-established approach to enhance the antibody titers and protective efficacy of several protein subunit vaccines. However, this approach has been less explored for mRNA LNP vaccines. Methods: Here, 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. Results: We compared multimerized antigen to monomeric secreted antigen and monomeric surface-displayed antigen and observed that the IMX313 domain efficiently multimerized mSb protein and significantly enhanced anti-mSb antibody titers, whereas the foldon and ferritin domains failed to multimerize or improve antibody levels. Conclusions: Our results extend the observation of improved immunogenicity from antigen multimerization to mRNA LNP vaccines and indicate that the 7-mer forming IMX313 multimerization domain may be an ideal candidate for multimer formation in the context of mRNA LNP vaccination. Future studies are needed to evaluate the multimerization of pathogen-derived antigens, in the mRNA LNP format, for the enhancement of neutralization and protective efficacy.