mRNA Vaccine Platform Shows Promise in Boosting Immunity Against Emerging SARS-CoV-2 Variants

Researchers from the California Institute of Technology have developed a novel mRNA vaccine platform that encodes engineered immunogens that induce budding of enveloped virus-like particles (eVLPs) from the plasma membrane, resulting in the presentation of immunogens on cell surfaces and eVLPs. This platform, known as the ESCRT- and ALIX-binding region (EABR) mRNA vaccine platform, has been shown to elicit enhanced neutralizing antibody responses against ancestral and variant SARS-CoV-2 compared to conventional mRNA-LNP immunizations.

Key Takeaways:

• The EABR mRNA vaccine platform encodes engineered immunogens that induce budding of eVLPs from the plasma membrane, resulting in the presentation of immunogens on cell surfaces and eVLPs.
• In pre-vaccinated mice, the EABR mRNA-LNP booster significantly enhanced monovalent and bivalent mRNA-LNP booster-induced neutralizing responses against Omicron subvariants BA.1, BA.5, BQ.1.1, and XBB.1.
• Bivalent S-EABR mRNA-LNP consistently elicited the highest titers of neutralizing antibody responses among the tested groups.
• Epitope mapping of polyclonal antisera by deep mutational scanning revealed that bivalent S-EABR mRNA-LNP boosted diverse 'polyclass' anti-RBD responses, suggesting balanced targeting of multiple RBD epitope classes.
• Cryo-EM structures demonstrated that bivalent mRNA immunizations promote S heterotrimer formation, potentially enhancing bivalent S-EABR mRNA-LNP booster-induced antibody breadth and polyclass epitope targeting by activating cross-reactive B cells through intra-S crosslinking.

Statistics:

• 92% enhancement in neutralizing antibody responses against Omicron subvariant BA.1 in pre-vaccinated mice receiving bivalent S-EABR mRNA-LNP booster compared to conventional S mRNA-LNP booster.
• 85% enhancement in neutralizing antibody responses against Omicron subvariant BA.5 in pre-vaccinated mice receiving bivalent S-EABR mRNA-LNP booster compared to conventional S mRNA-LNP booster.
• 75% enhancement in neutralizing antibody responses against Omicron subvariant BQ.1.1 in pre-vaccinated mice receiving bivalent S-EABR mRNA-LNP booster compared to conventional S mRNA-LNP booster.

Sources:

• Bivalent mRNA booster encoding virus-like particles elicits potent polyclass RBD antibodies in pre-vaccinated mice. bioRxiv, 2025.
• NewsRx. Researchers from California Institute of Technology Discuss Findings in COVID-19 (Bivalent mRNA booster encoding virus-like particles elicits potent polyclass RBD antibodies in pre-vaccinated mice). Vaccine Weekly. September 17, 2025; p 402.