High-Resolution Linear Epitope Mapping of the Receptor Binding Domain of SARS-CoV-2 Spike Protein in COVID-19 mRNA Vaccine Recipients
Open Access
- 10 November 2021
- journal article
- research article
- Published by American Society for Microbiology in Microbiology Spectrum
- Vol. 9 (3), e0096521
- https://doi.org/10.1128/spectrum.00965-21
Abstract
The prompt rollout of the severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) mRNA vaccine is facilitating population immunity, which is becoming more dominant than natural infection-mediated immunity. In the midst of coronavirus disease 2019 (COVID-19) vaccine deployment, understanding the epitope profiles of vaccine-elicited antibodies will be the first step in assessing the functionality of vaccine-induced immunity. In this study, the high-resolution linear epitope profiles of Pfizer-BioNTech COVID-19 mRNA vaccine recipients and COVID-19 patients were delineated by using microarrays mapped with overlapping peptides of the receptor binding domain (RBD) of the SARS-CoV-2 spike protein. The vaccine-induced antibodies targeting the RBD had a broader distribution across the RBD than that induced by the natural infection. Half-maximal neutralization titers were measured in vitro by live virus neutralization assays. As a result, relatively lower neutralizability was observed in vaccine recipient sera, when normalized to a total anti-RBD IgG titer. However, mutation panel assays targeting the SARS-CoV-2 variants of concern have shown that the vaccine-induced epitope variety, rich in breadth, may grant resistance against future viral evolutionary escapes, serving as an advantage of vaccine-induced immunity. IMPORTANCE Establishing vaccine-based population immunity has been the key factor in attaining herd protection. Thanks to expedited worldwide research efforts, the potency of mRNA vaccines against the coronavirus disease 2019 (COVID-19) is now incontestable. The next debate is regarding the coverage of SARS-CoV-2 variants. In the midst of vaccine deployment, it is of importance to describe the similarities and differences between the immune responses of COVID-19 vaccine recipients and naturally infected individuals. In this study, we demonstrated that the antibody profiles of vaccine recipients are richer in variety, targeting a key protein of the invading virus, than those of naturally infected individuals. Vaccine-elicited antibodies included more nonneutralizing antibodies than infection-elicited antibodies, and their breadth in antibody variations suggested possible resilience against future SARS-CoV-2 variants. The antibody profile achieved by vaccinations in naive individuals provides important insight into the first step toward vaccine-based population immunity.Keywords
Funding Information
- Japan Agency for Medical Research and Development (JP20wm0125003, JP20he1122001, JP20nk0101627)
- Japan Agency for Medical Research and Development (JP20jk0110021)
- MEXT | Japan Society for the Promotion of Science (JP21441824)
- Osaka City University (Special Reserves fund for COVID-19)
- Center for IPS Cell Research and Application, Kyoto University (COVID-19 Private Fund from the Shinya Yamanaka laboratory)
This publication has 46 references indexed in Scilit:
- Key residues of the receptor binding motif in the spike protein of SARS-CoV-2 that interact with ACE2 and neutralizing antibodiesCellular & Molecular Immunology, 2020
- A highly conserved cryptic epitope in the receptor binding domains of SARS-CoV-2 and SARS-CoVScience, 2020
- Structural basis of receptor recognition by SARS-CoV-2Nature, 2020
- Structure of the SARS-CoV-2 spike receptor-binding domain bound to the ACE2 receptorNature, 2020
- Recombinant Protein Containing B-Cell Epitopes of Different Loxosceles Spider Toxins Generates Neutralizing Antibodies in Immunized RabbitsFrontiers in Immunology, 2018
- Globular Head-Displayed Conserved Influenza H1 Hemagglutinin Stalk Epitopes Confer Protection against Heterologous H1N1 VirusPLOS ONE, 2016
- Human Monoclonal Antibodies Broadly Neutralizing against Influenza B VirusPLoS Pathogens, 2013
- Identification of IgE Binding to Api g 1‐Derived PeptidesChemBioChem, 2010
- Synthesis and Application of Peptide Arrays: Quo Vadis SPOT TechnologyChemBioChem, 2009
- Human Monoclonal Antibody Combination against SARS Coronavirus: Synergy and Coverage of Escape MutantsPLoS Medicine, 2006