Multivalent mRNA Vaccine Elicits Broad Protection against SARS-CoV-2 Variants of Concern
Author:
Kumari Monika1, Liang Kang-Hao2ORCID, Su Shih-Chieh1, Lin Hsiu-Ting1, Lu Yu-Feng1, Wu Ming-Jane1, Chen Wan-Yu1, Wu Han-Chung12ORCID
Affiliation:
1. Institute of Cellular and Organismic Biology, Academia Sinica, Taipei 11529, Taiwan 2. Biomedical Translation Research Center (BioTReC), Academia Sinica, Taipei 11529, Taiwan
Abstract
SARS-CoV-2 new waves are primarily caused by changes to the spike protein (S), which can substantially decrease the efficacy of vaccines. Therefore, we tested several multivalent mRNA-LNP vaccines, targeting the full-length S proteins of different variants, and identified an optimal combination for protection against VOCs in BALB/c mice. The tested formulations included trivalent (WT + BA.5 + XBB.1.5), pentavalent (WT + BA.5 + XBB.1.5 + BQ.1.1 + CH.1.1), and octavalent (WT + BA.5 + XBB.1.5 + BQ.1.1 + CH.1.1 + Alpha + Delta + BA.2) vaccines. Among these multivalent vaccines, the pentavalent vaccine showed superior protection for almost all tested variants. Despite this, each multivalent vaccine elicited greater broad-spectrum neutralizing antibodies than the previously evaluated bivalent vaccine (WT + BA.5). Subsequently, we redesigned the multivalent vaccine to efficiently generate neutralizing antibodies against recent VOCs, including EG.5.1. Immunization with the redesigned pentavalent vaccine (WT + EG.5.1 + XBB.1.16 + Delta + BA.5) showed moderate levels of protection against recent Omicron VOCs. Results suggest that the neutralization activity of multivalent vaccines is better than those of the tested bivalent vaccines against WT + BA.5 and WT + EG.5.1. Moreover, the pentavalent vaccine we developed may be highly useful for neutralizing new Omicron VOCs.
Funder
The Emerging Infectious and Major Disease Research Program
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