Multivalent mRNA Vaccine Elicits Broad Protection against SARS-CoV-2 Variants of Concern

Area of Science:

• Virology
• Immunology
• Vaccine Development

Background:

• Emerging SARS-CoV-2 variants with spike protein mutations reduce vaccine efficacy.
• Multivalent vaccines are being explored to address evolving viral threats.

Purpose of the Study:

• To evaluate the efficacy of multivalent mRNA-LNP vaccines against SARS-CoV-2 variants.
• To identify an optimal multivalent vaccine formulation for broad protection.

Main Methods:

• Testing of trivalent, pentavalent, and octavalent mRNA-LNP vaccines in BALB/c mice.
• Assessment of neutralizing antibody responses against various SARS-CoV-2 variants.
• Redesign and evaluation of a pentavalent vaccine against recent Omicron subvariants.

Main Results:

• The pentavalent vaccine (WT + BA.5 + XBB.1.5 + BQ.1.1 + CH.1.1) showed superior protection compared to other tested multivalent formulations.
• All tested multivalent vaccines induced broader neutralizing antibodies than a bivalent vaccine (WT + BA.5).
• A redesigned pentavalent vaccine (WT + EG.5.1 + XBB.1.16 + Delta + BA.5) provided moderate protection against recent Omicron VOCs.

Conclusions:

• Multivalent vaccines demonstrate enhanced neutralization activity against SARS-CoV-2 variants compared to bivalent vaccines.
• The developed pentavalent vaccine formulation shows promise for neutralizing emerging Omicron variants.