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Self-Multimerization of mRNA LNP-Derived Antigen Improves Antibody Responses
Cody A Despins1,2, James Round1, Lisa Dreolini1
1Department of Basic and Translational Research, BC Cancer Research Institute, 675 W 10th Ave, Vancouver, BC V5Z 1L3, Canada.
Vaccines
|January 28, 2026
Summary
Antigen multimerization enhances mRNA LNP vaccines. The IMX313 (7-mer) domain significantly boosted antibody titers against a model antigen, unlike other domains, showing promise for vaccine development.
Area of Science:
- Vaccinology
- Immunology
- Protein Engineering
Background:
- Lipid nanoparticle (LNP) encapsulated messenger RNA (mRNA) technology is a leading vaccine platform.
- Antigen multimerization is proven to boost protein subunit vaccine efficacy.
- Its application in mRNA LNP vaccines remains underexplored.
Purpose of the Study:
- To compare the efficacy of different antigen multimerization domains for mRNA LNP vaccines.
- To assess the impact of foldon (3-mer), IMX313 (7-mer), and ferritin (24-mer) domains on immunogenicity.
- To determine the optimal multimerization strategy for mRNA LNP vaccine development.
Main Methods:
- Utilized mStrawberry (mSb) as a model antigen in mRNA LNP vaccine formulations.
- Performed head-to-head comparison of foldon, IMX313, and ferritin multimerization domains in mice.
- Assessed antibody titers against the monomeric and multimerized antigen.
Main Results:
- The IMX313 (7-mer) domain successfully multimerized the mSb antigen.
- IMX313 significantly enhanced anti-mSb antibody titers compared to monomeric antigen.
- Foldon and ferritin domains failed to achieve effective multimerization or enhance antibody levels.
Conclusions:
- Antigen multimerization can improve immunogenicity in mRNA LNP vaccines.
- The IMX313 (7-mer) domain is a promising candidate for enhancing mRNA LNP vaccine efficacy.
- Further research should explore pathogen-derived antigens with IMX313 for improved neutralization and protection.
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