Abstract
Multiple SARS-CoV-2 variants are identified with higher rates of transmissibility or greater disease severity. Particularly, recent emergence of Omicron variant with rapid human-to-human transmission posts new challenges to the current prevention strategies. In this study, following vaccination with an mRNA vaccine encoding SARS-CoV-2 receptor-binding domain (RBD-mRNA), we detected serum antibodies that neutralized pseudoviruses expressing spike (S) protein harboring single or multiple mutations, as well as authentic SARS-CoV-2 variants, and evaluated its protection against SARS-CoV-2 infection. The vaccine induced durable antibodies that potently neutralized prototypic strain and B.1.1.7 lineage variant pseudoviruses containing N501Y or D614G mutations alone or in combination with a N439K mutation (B.1.258 lineage), with a L452R mutation (B.1.427 or B.1.429 lineage), or a L452R-E484Q double mutation (B.1.617.1 variant), although neutralizing activity against B.1.1.7 lineage variant containing 10 amino acid changes in the S protein was slightly reduced. The RBD-mRNA-induced antibodies exerted moderate neutralization against authentic B.1.617.2 and B.1.1.529 variants, and pseudotyped B.1.351 and P.1 lineage variants containing K417N/T, E484K, and N501Y mutations, the B.1.617.2 lineage variant harboring L452R, T478K, and P681R mutations, and the B.1.1.529 lineage variant containing 38 mutations in the S protein. Particularly, RBD-mRNA vaccine completely protected mice from challenge with a virulent mouse-adapted SARS-CoV-2 variant. Among these lineages, B.1.1.7, B.1.351, P.1, B.1.617.2, and B.1.1.529 belong to Alpha, Beta, Gamma, Delta, and Omicron variants, respectively. Our observations reveal that RBD-mRNA vaccine is promising and highlights the need to design novel vaccines with improved neutralization against current and future pandemic SARS-CoV-2 variants.
【초록키워드】 SARS-CoV-2, Vaccine, vaccination, pandemic, Mutation, antibody, mRNA vaccine, B.1.351, neutralization, SARS-COV-2 infection, disease severity, mutations, variant, SARS-CoV-2 variant, Delta, B.1.617.2, omicron, variants, B.1.1.7 lineage, Protein, Neutralizing activity, D614G mutation, Transmissibility, SARS-CoV-2 variants, B.1.427, L452R, B.1.1.7, mice, N501Y, P.1, B.1.617.1, Lineage, Gamma, B.1.429, E484K, Beta, serum antibody, B.1.1.529, P681R, lineages, moderate, N439K, Combination, mouse-adapted SARS-CoV-2, observation, T478K, domain, human-to-human transmission, multiple mutations, Multiple, virulent, pseudotyped, neutralized, highlight, greater, amino acid change, evaluated, reduced, the S protein, expressing, pseudovirus, 【제목키워드】 neutralizing antibody, SARS-CoV-2, Vaccine, omicron, mice, PROTECT, induce, other variant,