Publications
Research SquareSep 2023 DOI:
10.21203/rs.3.rs-3344007/v1

Enhanced Omicron subvariant cross-neutralization efficacy of a SARS-CoV-2 BA.4/5 mRNA vaccine encoding a noncleaved, nonfusogenic spike antigen

Oh, Jong-Won; Seo, Han Young; Jung, Haewon; Woo, Hawon; Jung, Hae-Gwang; Cho, Hee; Bak, Yeonju; Lee, Se-Young; Son, Yu-Min; Yoon, Gone; Hwang, Seo-Yeon; Park, Inho; Shin, Jeon-Soo
Product Used
NGS
Abstract
The rapid emergence of diverse SARS-CoV-2 variants, notably the Omicron variant, poses challenges to vaccine development. Here, we present a noncleaved, nonfusogenic spike (S) protein eliciting robust B- and T-cell immune responses against Omicron BA.5. The antigen incorporates the R685S and R815A mutations, effectively preventing the shedding of the S1 subunit and eliminating fusogenic activity of the resulting S antigen, termed S(SA). Through reverse genetic analysis, we found that the noncleaved form S protein with the R685S mutation enhances ACE2-dependent viral entry in vitro compared to the wild-type S protein, without increasing the virulence of the mutant virus in mice. The mRNA vaccine encoding the Omicron BA.4/5 S(SA) antigen conferred protective immunity in mice following two doses of 1 mg Ψ-UTP- or UTP-incorporated mRNA vaccines. Despite a roughly 6-fold reduction in neutralizing potency, both mRNA vaccines exhibited broad neutralizing efficacy against Omicron subvariants, including the XBB lineage variants XBB.1.5 and XBB.1.16.
Product Used
NGS

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