Journal article
A Glycosylated RBD Protein Induces Enhanced Neutralizing Antibodies against Omicron and Other Variants with Improved Protection against SARS-CoV-2 Infection
Journal of virology, Vol.96(17), e00118-22
08/16/2022
DOI: 10.1128/jvi.00118-22
PMCID: PMC9472618
PMID: 35972290
Abstract
SARS-CoV-2 has mutated frequently since its first emergence in 2019. Numerous variants, including the currently emerging Omicron variant, have demonstrated high transmissibility or increased disease severity, posing serious threats to global public health. This study describes the identification of an immunodominant non-neutralizing epitope on SARS-CoV-2 receptor-binding domain (RBD). A subunit vaccine against this mutant RBD, constructed by masking this epitope with a glycan probe, did not significantly affect RBD’s receptor-binding affinity or antibody-binding affinity, or its ability to induce antibody production. However, this vaccine enhanced the neutralizing activity of this RBD and its protective efficacy in immunized mice. Specifically, this vaccine elicited significantly higher-titer neutralizing antibodies than the prototypic RBD protein against Alpha (B.1.1.7 lineage), Beta (B.1.351 lineage), Gamma (P.1 lineage), and Epsilon (B.1.427 or B.1.429 lineage) variant pseudoviruses containing single or combined mutations in the spike (S) protein, albeit the neutralizing antibody titers against some variants were slightly lower than against original SARS-CoV-2. This vaccine also significantly improved the neutralizing activity of the prototypic RBD against pseudotyped and authentic Delta (B.1.617.2 lineage) and Omicron (B.1.1.529 lineage) variants, although the neutralizing antibody titers were lower than against original SARS-CoV-2. In contrast to the prototypic RBD, the mutant RBD completely protected human ACE2 (hACE2)-transgenic mice from lethal challenge with a prototype SARS-CoV-2 strain and a Delta variant without weight loss. Overall, these findings indicate that this RBD vaccine has broad-spectrum activity against multiple SARS-CoV-2 variants, as well as the potential to be effective and have improved efficacy against Omicron and other pandemic variants. IMPORTANCE Several SARS-CoV-2 variants have shown increased transmissibility, calling for a need to develop effective vaccines with broadly neutralizing activity against multiple variants. This study identified a non-neutralizing epitope on the receptor-binding domain (RBD) of SARS-CoV-2 spike protein, and further shielded it with a glycan probe. A subunit vaccine based on this mutant RBD significantly enhanced the ability of prototypic RBD against multiple SARS-CoV-2 variants, including the Delta and Omicron strains, although the neutralizing antibody titers against some of these variants were lower than those against original SARS-CoV-2. This mutant vaccine also enhanced the protective efficacy of the prototypic RBD vaccine against SARS-CoV-2 infection in immunized animals. In conclusion, this study identified an engineered RBD vaccine against Omicron and other SARS-CoV-2 variants that induced stronger neutralizing antibodies and protection than the original RBD vaccine. It also highlights the need to improve the effectiveness of current COVID-19 vaccines to prevent pandemic SARS-CoV-2 variants.
Details
- Title: Subtitle
- A Glycosylated RBD Protein Induces Enhanced Neutralizing Antibodies against Omicron and Other Variants with Improved Protection against SARS-CoV-2 Infection
- Creators
- Juan Shi - New York Blood CenterJian Zheng - University of IowaWanbo Tai - New York Blood CenterAbhishek K. Verma - University of IowaXiujuan ZhangQibin Geng - University of MinnesotaGang Wang - Georgia State UniversityXiaoqing Guan - Georgia State UniversityMoffat M. Malisheni - Georgia State UniversityAbby E. Odle - University of IowaWei Zhang - University of MinnesotaFang Li - University of MinnesotaStanley Perlman - University of IowaLanying Du - New York Blood Center
- Contributors
- Stacey Schultz-Cherry (Editor)
- Resource Type
- Journal article
- Publication Details
- Journal of virology, Vol.96(17), e00118-22
- Publisher
- American Society for Microbiology
- DOI
- 10.1128/jvi.00118-22
- PMID
- 35972290
- PMCID
- PMC9472618
- ISSN
- 0022-538X
- eISSN
- 1098-5514
- Number of pages
- 12
- Grant note
- R01AI137472 / HHS | National Institutes of Health (NIH) (https://doi.org/10.13039/100000002) R01AI157975 / HHS | National Institutes of Health (NIH) (https://doi.org/10.13039/100000002) R01AI139092 / HHS | National Institutes of Health (NIH) (https://doi.org/10.13039/100000002)
- Language
- English
- Date published
- 08/16/2022
- Academic Unit
- Microbiology and Immunology; Stead Family Department of Pediatrics; Iowa Neuroscience Institute; Infectious Disease (Pediatrics)
- Record Identifier
- 9984283459802771
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