RBD-mRNA vaccine induces broadly neutralizing antibodies against Omicron and multiple other variants and protects mice from SARS-CoV-2 challenge

Juan Shi; Jian Zheng; Xiujuan Zhang; Wanbo Tai; Abby E Odle; Stanley Perlman; Lanying Du

doi:10.1016/j.trsl.2022.04.007

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RBD-mRNA vaccine induces broadly neutralizing antibodies against Omicron and multiple other variants and protects mice from SARS-CoV-2 challenge

Journal article

Open access

Peer reviewed

RBD-mRNA vaccine induces broadly neutralizing antibodies against Omicron and multiple other variants and protects mice from SARS-CoV-2 challenge

Juan Shi, Jian Zheng, Xiujuan Zhang, Wanbo Tai, Abby E Odle, Stanley Perlman and Lanying Du

Translational research : the journal of laboratory and clinical medicine, Vol.248, pp.11-21

04/27/2022

DOI: 10.1016/j.trsl.2022.04.007

PMCID: PMC9045870

PMID: 35489692

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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.

Coronavirus

COVID-19

Durable and broadly neutralizing antibodies

mRNA vaccine

Multiple variants

Omicron and Delta variants

Protection

SARS-CoV-2

Details

Title: Subtitle: RBD-mRNA vaccine induces broadly neutralizing antibodies against Omicron and multiple other variants and protects mice from SARS-CoV-2 challenge
Creators: Juan Shi - New York Blood Center
Jian Zheng - University of Iowa
Xiujuan Zhang - New York Blood Center
Wanbo Tai - New York Blood Center
Abby E Odle - University of Iowa
Stanley Perlman - University of Iowa
Lanying Du - New York Blood Center
Resource Type: Journal article
Publication Details: Translational research : the journal of laboratory and clinical medicine, Vol.248, pp.11-21
DOI: 10.1016/j.trsl.2022.04.007
PMID: 35489692
PMCID: PMC9045870
NLM abbreviation: Transl Res
ISSN: 1931-5244
eISSN: 1878-1810
Publisher: Elsevier Inc
Grant note: DOI: 10.13039/100000002, name: National Institutes of Health, award: R01AI137472, R01AI139092, R01AI157975
Language: English
Date published: 04/27/2022
Academic Unit: Microbiology and Immunology; Stead Family Department of Pediatrics; Iowa Neuroscience Institute; Infectious Disease (Pediatrics)
Record Identifier: 9984256060102771

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