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High-Resolution Linear Epitope Mapping of the Receptor Binding Domain of SARS-CoV-2 Spike Protein in COVID-19 mRNA Vaccine Recipients.
Microbiol Spectr. 2021 12 22; 9(3):e0096521.MS

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.

Authors+Show Affiliations

Department of Parasitology & Research Center for Infectious Disease Sciences, Graduate School of Medicine, Osaka City Universitygrid.261445.0, Osaka, Japan.Department of Parasitology & Research Center for Infectious Disease Sciences, Graduate School of Medicine, Osaka City Universitygrid.261445.0, Osaka, Japan.Department of Parasitology & Research Center for Infectious Disease Sciences, Graduate School of Medicine, Osaka City Universitygrid.261445.0, Osaka, Japan.Department of Parasitology & Research Center for Infectious Disease Sciences, Graduate School of Medicine, Osaka City Universitygrid.261445.0, Osaka, Japan.Department of Parasitology & Research Center for Infectious Disease Sciences, Graduate School of Medicine, Osaka City Universitygrid.261445.0, Osaka, Japan.Department of Parasitology & Research Center for Infectious Disease Sciences, Graduate School of Medicine, Osaka City Universitygrid.261445.0, Osaka, Japan.Department of Parasitology & Research Center for Infectious Disease Sciences, Graduate School of Medicine, Osaka City Universitygrid.261445.0, Osaka, Japan.Department of Traumatology and Critical Care Medicine, Graduate School of Medicine, Osaka City Universitygrid.261445.0, Osaka, Japan.Department of Traumatology and Critical Care Medicine, Graduate School of Medicine, Osaka City Universitygrid.261445.0, Osaka, Japan.Department of Infection Control Science, Graduate School of Medicine, Osaka City Universitygrid.261445.0, Osaka, Japan.Department of Veterinary Science, Graduate School of Life and Environmental Sciences, Osaka Prefecture Universitygrid.261455.1, Izumisano, Osaka, Japan. Osaka International Research Center for Infectious Diseases, Osaka Prefecture Universitygrid.261455.1, Izumisano, Osaka, Japan. Asian Health Science Research Institute, Osaka Prefecture Universitygrid.261455.1, Izumisano, Osaka, Japan.Department of Parasitology & Research Center for Infectious Disease Sciences, Graduate School of Medicine, Osaka City Universitygrid.261445.0, Osaka, Japan.

Pub Type(s)

Journal Article
Research Support, Non-U.S. Gov't

Language

eng

PubMed ID

34756082

Citation

Nitahara, Yuko, et al. "High-Resolution Linear Epitope Mapping of the Receptor Binding Domain of SARS-CoV-2 Spike Protein in COVID-19 mRNA Vaccine Recipients." Microbiology Spectrum, vol. 9, no. 3, 2021, pp. e0096521.
Nitahara Y, Nakagama Y, Kaku N, et al. High-Resolution Linear Epitope Mapping of the Receptor Binding Domain of SARS-CoV-2 Spike Protein in COVID-19 mRNA Vaccine Recipients. Microbiol Spectr. 2021;9(3):e0096521.
Nitahara, Y., Nakagama, Y., Kaku, N., Candray, K., Michimuko, Y., Tshibangu-Kabamba, E., Kaneko, A., Yamamoto, H., Mizobata, Y., Kakeya, H., Yasugi, M., & Kido, Y. (2021). High-Resolution Linear Epitope Mapping of the Receptor Binding Domain of SARS-CoV-2 Spike Protein in COVID-19 mRNA Vaccine Recipients. Microbiology Spectrum, 9(3), e0096521. https://doi.org/10.1128/Spectrum.00965-21
Nitahara Y, et al. High-Resolution Linear Epitope Mapping of the Receptor Binding Domain of SARS-CoV-2 Spike Protein in COVID-19 mRNA Vaccine Recipients. Microbiol Spectr. 2021 12 22;9(3):e0096521. PubMed PMID: 34756082.
* Article titles in AMA citation format should be in sentence-case
TY - JOUR T1 - High-Resolution Linear Epitope Mapping of the Receptor Binding Domain of SARS-CoV-2 Spike Protein in COVID-19 mRNA Vaccine Recipients. AU - Nitahara,Yuko, AU - Nakagama,Yu, AU - Kaku,Natsuko, AU - Candray,Katherine, AU - Michimuko,Yu, AU - Tshibangu-Kabamba,Evariste, AU - Kaneko,Akira, AU - Yamamoto,Hiromasa, AU - Mizobata,Yasumitsu, AU - Kakeya,Hiroshi, AU - Yasugi,Mayo, AU - Kido,Yasutoshi, Y1 - 2021/11/10/ PY - 2021/11/11/pubmed PY - 2022/1/6/medline PY - 2021/11/10/entrez KW - COVID-19 KW - RBD KW - SARS-CoV-2 KW - immunoserology KW - neutralizing antibodies KW - serology KW - spike KW - spike protein SP - e0096521 EP - e0096521 JF - Microbiology spectrum JO - Microbiol Spectr VL - 9 IS - 3 N2 - 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. SN - 2165-0497 UR - https://www.unboundmedicine.com/medline/citation/34756082/High_Resolution_Linear_Epitope_Mapping_of_the_Receptor_Binding_Domain_of_SARS_CoV_2_Spike_Protein_in_COVID_19_mRNA_Vaccine_Recipients_ DB - PRIME DP - Unbound Medicine ER -