SARS-CoV-2 spike-reactive naïve B cells and pre-existing memory B cells contribute to antibody responses in unexposed individuals after vaccination
IntroductionSince December 2019, the emergence of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) causing coronavirus disease 2019 (COVID-19) has presented considerable public health challenges. Multiple vaccines have been used to induce neutralizing antibodies (nAbs) and memory B-cell...
| Main Authors: | , , , , , , , , , , , , , |
|---|---|
| Format: | Article |
| Language: | English |
| Published: |
Frontiers Media S.A.
2024-02-01
|
| Series: | Frontiers in Immunology |
| Subjects: | |
| Online Access: | https://www.frontiersin.org/articles/10.3389/fimmu.2024.1355949/full |
| _version_ | 1797311674466697216 |
|---|---|
| author | Shishan Teng Shishan Teng Yabin Hu Yabin Hu You Wang You Wang Yinggen Tang Yinggen Tang Qian Wu Xingyu Zheng Xingyu Zheng Rui Lu Rui Lu Dong Pan Dong Pan Fen Liu Fen Liu Tianyi Xie Tianyi Xie Chanfeng Wu Chanfeng Wu Yi-Ping Li Wenpei Liu Xiaowang Qu |
| author_facet | Shishan Teng Shishan Teng Yabin Hu Yabin Hu You Wang You Wang Yinggen Tang Yinggen Tang Qian Wu Xingyu Zheng Xingyu Zheng Rui Lu Rui Lu Dong Pan Dong Pan Fen Liu Fen Liu Tianyi Xie Tianyi Xie Chanfeng Wu Chanfeng Wu Yi-Ping Li Wenpei Liu Xiaowang Qu |
| author_sort | Shishan Teng |
| collection | DOAJ |
| description | IntroductionSince December 2019, the emergence of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) causing coronavirus disease 2019 (COVID-19) has presented considerable public health challenges. Multiple vaccines have been used to induce neutralizing antibodies (nAbs) and memory B-cell responses against the viral spike (S) glycoprotein, and many essential epitopes have been defined. Previous reports have identified severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) spike-reactive naïve B cells and preexisting memory B cells in unexposed individuals. However, the role of these spike-reactive B cells in vaccine-induced immunity remains unknown.MethodsTo elucidate the characteristics of preexisting SARS-CoV-2 S-reactive B cells as well as their maturation after antigen encounter, we assessed the relationship of spike-reactive B cells before and after vaccination in unexposed human individuals. We further characterized the sequence identity, targeting domain, broad-spectrum binding activity and neutralizing activity of these SARS-CoV-2 S-reactive B cells by isolating monoclonal antibodies (mAbs) from these B cells.ResultsThe frequencies of both spike-reactive naïve B cells and preexisting memory B cells before vaccination correlated with the frequencies of spike-reactive memory B cells after vaccination. Isolated mAbs from spike-reactive naïve B cells before vaccination had fewer somatic hypermutations (SHMs) than mAbs isolated from spike-reactive memory B cells before and after vaccination, but bound SARS-CoV-2 spike in vitro. Intriguingly, these germline-like mAbs possessed broad binding profiles for SARS-CoV-2 and its variants, although with low or no neutralizing capacity. According to tracking of the evolution of IGHV4-4/IGKV3-20 lineage antibodies from a single donor, the lineage underwent SHMs and developed increased binding activity after vaccination.DiscussionOur findings suggest that spike-reactive naïve B cells can be expanded and matured by vaccination and cocontribute to vaccine-elicited antibody responses with preexisting memory B cells. Selectively and precisely targeting spike-reactive B cells by rational antigen design may provide a novel strategy for next-generation SARS-CoV-2 vaccine development. |
| first_indexed | 2024-03-08T02:03:06Z |
| format | Article |
| id | doaj.art-c61c3fdf39a2460ba532924d3cf6ccfb |
| institution | Directory Open Access Journal |
| issn | 1664-3224 |
| language | English |
| last_indexed | 2024-03-08T02:03:06Z |
| publishDate | 2024-02-01 |
| publisher | Frontiers Media S.A. |
| record_format | Article |
| series | Frontiers in Immunology |
| spelling | doaj.art-c61c3fdf39a2460ba532924d3cf6ccfb2024-02-14T04:48:55ZengFrontiers Media S.A.Frontiers in Immunology1664-32242024-02-011510.3389/fimmu.2024.13559491355949SARS-CoV-2 spike-reactive naïve B cells and pre-existing memory B cells contribute to antibody responses in unexposed individuals after vaccinationShishan Teng0Shishan Teng1Yabin Hu2Yabin Hu3You Wang4You Wang5Yinggen Tang6Yinggen Tang7Qian Wu8Xingyu Zheng9Xingyu Zheng10Rui Lu11Rui Lu12Dong Pan13Dong Pan14Fen Liu15Fen Liu16Tianyi Xie17Tianyi Xie18Chanfeng Wu19Chanfeng Wu20Yi-Ping Li21Wenpei Liu22Xiaowang Qu23School of Public Health & School of Basic Medicine Sciences, Hengyang Medical School & Ministry of Education Key Laboratory of Rare Pediatric Diseases, University of South China, Hengyang, ChinaTranslational Medicine Institute, The First People’s Hospital of Chenzhou, Hengyang Medical School, University of South China, Chenzhou, ChinaSchool of Public Health & School of Basic Medicine Sciences, Hengyang Medical School & Ministry of Education Key Laboratory of Rare Pediatric Diseases, University of South China, Hengyang, ChinaTranslational Medicine Institute, The First People’s Hospital of Chenzhou, Hengyang Medical School, University of South China, Chenzhou, ChinaSchool of Public Health & School of Basic Medicine Sciences, Hengyang Medical School & Ministry of Education Key Laboratory of Rare Pediatric Diseases, University of South China, Hengyang, ChinaTranslational Medicine Institute, The First People’s Hospital of Chenzhou, Hengyang Medical School, University of South China, Chenzhou, ChinaSchool of Public Health & School of Basic Medicine Sciences, Hengyang Medical School & Ministry of Education Key Laboratory of Rare Pediatric Diseases, University of South China, Hengyang, ChinaTranslational Medicine Institute, The First People’s Hospital of Chenzhou, Hengyang Medical School, University of South China, Chenzhou, ChinaInstitute of Human Virology, Zhongshan School of Medicine, and Key Laboratory of Tropical Disease Control of the Ministry of Education, Sun Yat-sen University, Guangzhou, ChinaSchool of Public Health & School of Basic Medicine Sciences, Hengyang Medical School & Ministry of Education Key Laboratory of Rare Pediatric Diseases, University of South China, Hengyang, ChinaTranslational Medicine Institute, The First People’s Hospital of Chenzhou, Hengyang Medical School, University of South China, Chenzhou, ChinaSchool of Public Health & School of Basic Medicine Sciences, Hengyang Medical School & Ministry of Education Key Laboratory of Rare Pediatric Diseases, University of South China, Hengyang, ChinaTranslational Medicine Institute, The First People’s Hospital of Chenzhou, Hengyang Medical School, University of South China, Chenzhou, ChinaSchool of Public Health & School of Basic Medicine Sciences, Hengyang Medical School & Ministry of Education Key Laboratory of Rare Pediatric Diseases, University of South China, Hengyang, ChinaTranslational Medicine Institute, The First People’s Hospital of Chenzhou, Hengyang Medical School, University of South China, Chenzhou, ChinaSchool of Public Health & School of Basic Medicine Sciences, Hengyang Medical School & Ministry of Education Key Laboratory of Rare Pediatric Diseases, University of South China, Hengyang, ChinaTranslational Medicine Institute, The First People’s Hospital of Chenzhou, Hengyang Medical School, University of South China, Chenzhou, ChinaSchool of Public Health & School of Basic Medicine Sciences, Hengyang Medical School & Ministry of Education Key Laboratory of Rare Pediatric Diseases, University of South China, Hengyang, ChinaTranslational Medicine Institute, The First People’s Hospital of Chenzhou, Hengyang Medical School, University of South China, Chenzhou, ChinaSchool of Public Health & School of Basic Medicine Sciences, Hengyang Medical School & Ministry of Education Key Laboratory of Rare Pediatric Diseases, University of South China, Hengyang, ChinaTranslational Medicine Institute, The First People’s Hospital of Chenzhou, Hengyang Medical School, University of South China, Chenzhou, ChinaInstitute of Human Virology, Zhongshan School of Medicine, and Key Laboratory of Tropical Disease Control of the Ministry of Education, Sun Yat-sen University, Guangzhou, ChinaSchool of Public Health & School of Basic Medicine Sciences, Hengyang Medical School & Ministry of Education Key Laboratory of Rare Pediatric Diseases, University of South China, Hengyang, ChinaSchool of Public Health & School of Basic Medicine Sciences, Hengyang Medical School & Ministry of Education Key Laboratory of Rare Pediatric Diseases, University of South China, Hengyang, ChinaIntroductionSince December 2019, the emergence of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) causing coronavirus disease 2019 (COVID-19) has presented considerable public health challenges. Multiple vaccines have been used to induce neutralizing antibodies (nAbs) and memory B-cell responses against the viral spike (S) glycoprotein, and many essential epitopes have been defined. Previous reports have identified severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) spike-reactive naïve B cells and preexisting memory B cells in unexposed individuals. However, the role of these spike-reactive B cells in vaccine-induced immunity remains unknown.MethodsTo elucidate the characteristics of preexisting SARS-CoV-2 S-reactive B cells as well as their maturation after antigen encounter, we assessed the relationship of spike-reactive B cells before and after vaccination in unexposed human individuals. We further characterized the sequence identity, targeting domain, broad-spectrum binding activity and neutralizing activity of these SARS-CoV-2 S-reactive B cells by isolating monoclonal antibodies (mAbs) from these B cells.ResultsThe frequencies of both spike-reactive naïve B cells and preexisting memory B cells before vaccination correlated with the frequencies of spike-reactive memory B cells after vaccination. Isolated mAbs from spike-reactive naïve B cells before vaccination had fewer somatic hypermutations (SHMs) than mAbs isolated from spike-reactive memory B cells before and after vaccination, but bound SARS-CoV-2 spike in vitro. Intriguingly, these germline-like mAbs possessed broad binding profiles for SARS-CoV-2 and its variants, although with low or no neutralizing capacity. According to tracking of the evolution of IGHV4-4/IGKV3-20 lineage antibodies from a single donor, the lineage underwent SHMs and developed increased binding activity after vaccination.DiscussionOur findings suggest that spike-reactive naïve B cells can be expanded and matured by vaccination and cocontribute to vaccine-elicited antibody responses with preexisting memory B cells. Selectively and precisely targeting spike-reactive B cells by rational antigen design may provide a novel strategy for next-generation SARS-CoV-2 vaccine development.https://www.frontiersin.org/articles/10.3389/fimmu.2024.1355949/fullSARS-CoV-2naïve B cellpreexisting memory B cellvaccinationmonoclonal antibody |
| spellingShingle | Shishan Teng Shishan Teng Yabin Hu Yabin Hu You Wang You Wang Yinggen Tang Yinggen Tang Qian Wu Xingyu Zheng Xingyu Zheng Rui Lu Rui Lu Dong Pan Dong Pan Fen Liu Fen Liu Tianyi Xie Tianyi Xie Chanfeng Wu Chanfeng Wu Yi-Ping Li Wenpei Liu Xiaowang Qu SARS-CoV-2 spike-reactive naïve B cells and pre-existing memory B cells contribute to antibody responses in unexposed individuals after vaccination Frontiers in Immunology SARS-CoV-2 naïve B cell preexisting memory B cell vaccination monoclonal antibody |
| title | SARS-CoV-2 spike-reactive naïve B cells and pre-existing memory B cells contribute to antibody responses in unexposed individuals after vaccination |
| title_full | SARS-CoV-2 spike-reactive naïve B cells and pre-existing memory B cells contribute to antibody responses in unexposed individuals after vaccination |
| title_fullStr | SARS-CoV-2 spike-reactive naïve B cells and pre-existing memory B cells contribute to antibody responses in unexposed individuals after vaccination |
| title_full_unstemmed | SARS-CoV-2 spike-reactive naïve B cells and pre-existing memory B cells contribute to antibody responses in unexposed individuals after vaccination |
| title_short | SARS-CoV-2 spike-reactive naïve B cells and pre-existing memory B cells contribute to antibody responses in unexposed individuals after vaccination |
| title_sort | sars cov 2 spike reactive naive b cells and pre existing memory b cells contribute to antibody responses in unexposed individuals after vaccination |
| topic | SARS-CoV-2 naïve B cell preexisting memory B cell vaccination monoclonal antibody |
| url | https://www.frontiersin.org/articles/10.3389/fimmu.2024.1355949/full |
| work_keys_str_mv | AT shishanteng sarscov2spikereactivenaivebcellsandpreexistingmemorybcellscontributetoantibodyresponsesinunexposedindividualsaftervaccination AT shishanteng sarscov2spikereactivenaivebcellsandpreexistingmemorybcellscontributetoantibodyresponsesinunexposedindividualsaftervaccination AT yabinhu sarscov2spikereactivenaivebcellsandpreexistingmemorybcellscontributetoantibodyresponsesinunexposedindividualsaftervaccination AT yabinhu sarscov2spikereactivenaivebcellsandpreexistingmemorybcellscontributetoantibodyresponsesinunexposedindividualsaftervaccination AT youwang sarscov2spikereactivenaivebcellsandpreexistingmemorybcellscontributetoantibodyresponsesinunexposedindividualsaftervaccination AT youwang sarscov2spikereactivenaivebcellsandpreexistingmemorybcellscontributetoantibodyresponsesinunexposedindividualsaftervaccination AT yinggentang sarscov2spikereactivenaivebcellsandpreexistingmemorybcellscontributetoantibodyresponsesinunexposedindividualsaftervaccination AT yinggentang sarscov2spikereactivenaivebcellsandpreexistingmemorybcellscontributetoantibodyresponsesinunexposedindividualsaftervaccination AT qianwu sarscov2spikereactivenaivebcellsandpreexistingmemorybcellscontributetoantibodyresponsesinunexposedindividualsaftervaccination AT xingyuzheng sarscov2spikereactivenaivebcellsandpreexistingmemorybcellscontributetoantibodyresponsesinunexposedindividualsaftervaccination AT xingyuzheng sarscov2spikereactivenaivebcellsandpreexistingmemorybcellscontributetoantibodyresponsesinunexposedindividualsaftervaccination AT ruilu sarscov2spikereactivenaivebcellsandpreexistingmemorybcellscontributetoantibodyresponsesinunexposedindividualsaftervaccination AT ruilu sarscov2spikereactivenaivebcellsandpreexistingmemorybcellscontributetoantibodyresponsesinunexposedindividualsaftervaccination AT dongpan sarscov2spikereactivenaivebcellsandpreexistingmemorybcellscontributetoantibodyresponsesinunexposedindividualsaftervaccination AT dongpan sarscov2spikereactivenaivebcellsandpreexistingmemorybcellscontributetoantibodyresponsesinunexposedindividualsaftervaccination AT fenliu sarscov2spikereactivenaivebcellsandpreexistingmemorybcellscontributetoantibodyresponsesinunexposedindividualsaftervaccination AT fenliu sarscov2spikereactivenaivebcellsandpreexistingmemorybcellscontributetoantibodyresponsesinunexposedindividualsaftervaccination AT tianyixie sarscov2spikereactivenaivebcellsandpreexistingmemorybcellscontributetoantibodyresponsesinunexposedindividualsaftervaccination AT tianyixie sarscov2spikereactivenaivebcellsandpreexistingmemorybcellscontributetoantibodyresponsesinunexposedindividualsaftervaccination AT chanfengwu sarscov2spikereactivenaivebcellsandpreexistingmemorybcellscontributetoantibodyresponsesinunexposedindividualsaftervaccination AT chanfengwu sarscov2spikereactivenaivebcellsandpreexistingmemorybcellscontributetoantibodyresponsesinunexposedindividualsaftervaccination AT yipingli sarscov2spikereactivenaivebcellsandpreexistingmemorybcellscontributetoantibodyresponsesinunexposedindividualsaftervaccination AT wenpeiliu sarscov2spikereactivenaivebcellsandpreexistingmemorybcellscontributetoantibodyresponsesinunexposedindividualsaftervaccination AT xiaowangqu sarscov2spikereactivenaivebcellsandpreexistingmemorybcellscontributetoantibodyresponsesinunexposedindividualsaftervaccination |