tetano
Editor, Senior Moderator
Front Immunol
. 2024 Feb 14:15:1355949.
doi: 10.3389/fimmu.2024.1355949. eCollection 2024. SARS-CoV-2 spike-reactive naïve B cells and pre-existing memory B cells contribute to antibody responses in unexposed individuals after vaccination
Shishan Teng[SUP] 1 2 [/SUP], Yabin Hu[SUP] 1 2 [/SUP], You Wang[SUP] 1 2 [/SUP], Yinggen Tang[SUP] 1 2 [/SUP], Qian Wu[SUP] 3 [/SUP], Xingyu Zheng[SUP] 1 2 [/SUP], Rui Lu[SUP] 1 2 [/SUP], Dong Pan[SUP] 1 2 [/SUP], Fen Liu[SUP] 1 2 [/SUP], Tianyi Xie[SUP] 1 2 [/SUP], Chanfeng Wu[SUP] 1 2 [/SUP], Yi-Ping Li[SUP] 3 [/SUP], Wenpei Liu[SUP] 1 [/SUP], Xiaowang Qu[SUP] 1 [/SUP]
Affiliations
Introduction: Since 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.
Methods: To 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.
Results: The 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.
Discussion: Our 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.
Keywords: SARS-CoV-2; monoclonal antibody; naïve B cell; preexisting memory B cell; vaccination.
. 2024 Feb 14:15:1355949.
doi: 10.3389/fimmu.2024.1355949. eCollection 2024. SARS-CoV-2 spike-reactive naïve B cells and pre-existing memory B cells contribute to antibody responses in unexposed individuals after vaccination
Shishan Teng[SUP] 1 2 [/SUP], Yabin Hu[SUP] 1 2 [/SUP], You Wang[SUP] 1 2 [/SUP], Yinggen Tang[SUP] 1 2 [/SUP], Qian Wu[SUP] 3 [/SUP], Xingyu Zheng[SUP] 1 2 [/SUP], Rui Lu[SUP] 1 2 [/SUP], Dong Pan[SUP] 1 2 [/SUP], Fen Liu[SUP] 1 2 [/SUP], Tianyi Xie[SUP] 1 2 [/SUP], Chanfeng Wu[SUP] 1 2 [/SUP], Yi-Ping Li[SUP] 3 [/SUP], Wenpei Liu[SUP] 1 [/SUP], Xiaowang Qu[SUP] 1 [/SUP]
Affiliations
- PMID: 38420128
- PMCID: PMC10899457
- DOI: 10.3389/fimmu.2024.1355949
Introduction: Since 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.
Methods: To 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.
Results: The 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.
Discussion: Our 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.
Keywords: SARS-CoV-2; monoclonal antibody; naïve B cell; preexisting memory B cell; vaccination.