tetano
Editor, Senior Moderator
Front Immunol
. 2024 Jun 21:15:1406138.
doi: 10.3389/fimmu.2024.1406138. eCollection 2024. Heterologous booster vaccination enhances antibody responses to SARS-CoV-2 by improving Tfh function and increasing B-cell clonotype SHM frequency
Yanli Song[SUP] 1 [/SUP], Jiaolei Wang[SUP] 2 [/SUP], Zhihui Yang[SUP] 1 [/SUP], Qian He[SUP] 2 [/SUP], Chunting Bao[SUP] 2 [/SUP], Ying Xie[SUP] 2 [/SUP], Yufang Sun[SUP] 2 [/SUP], Shuyan Li[SUP] 2 [/SUP], Yaru Quan[SUP] 2 [/SUP], Huijie Yang[SUP] 2 [/SUP], Changgui Li[SUP] 2 [/SUP]
Affiliations
Heterologous prime-boost has broken the protective immune response bottleneck of the COVID-19 vaccines. however, the underlying mechanisms have not been fully elucidated. Here, we investigated antibody responses and explored the response of germinal center (GC) to priming with inactivated vaccines and boosting with heterologous adenoviral-vectored vaccines or homologous inactivated vaccines in mice. Antibody responses were dramatically enhanced by both boosting regimens. Heterologous immunization induced more robust GC activation, characterized by increased Tfh cell populations and enhanced helper function. Additionally, increased B-cell activation and antibody production were observed in a heterologous regimen. Libra-seq was used to compare the differences of S1-, S2- and NTD-specific B cells between homologous and heterologous vaccination, respectively. S2-specific CD19+ B cells presented increased somatic hypermutations (SHMs), which were mainly enriched in plasma cells. Moreover, a heterologous booster dose promoted the clonal expansion of B cells specific to S2 and NTD regions. In conclusion, the functional role of Tfh and B cells following SARS-CoV-2 heterologous vaccination may be important for modulating antibody responses. These findings provide new insights for the development of SARS-CoV-2 vaccines that induce more robust antibody response.
Keywords: Libra-seq; SARS-CoV-2; SHM; Tfh cells; germinal center; heterologous; homologous.
. 2024 Jun 21:15:1406138.
doi: 10.3389/fimmu.2024.1406138. eCollection 2024. Heterologous booster vaccination enhances antibody responses to SARS-CoV-2 by improving Tfh function and increasing B-cell clonotype SHM frequency
Yanli Song[SUP] 1 [/SUP], Jiaolei Wang[SUP] 2 [/SUP], Zhihui Yang[SUP] 1 [/SUP], Qian He[SUP] 2 [/SUP], Chunting Bao[SUP] 2 [/SUP], Ying Xie[SUP] 2 [/SUP], Yufang Sun[SUP] 2 [/SUP], Shuyan Li[SUP] 2 [/SUP], Yaru Quan[SUP] 2 [/SUP], Huijie Yang[SUP] 2 [/SUP], Changgui Li[SUP] 2 [/SUP]
Affiliations
- PMID: 38975334
- PMCID: PMC11224535
- DOI: 10.3389/fimmu.2024.1406138
Heterologous prime-boost has broken the protective immune response bottleneck of the COVID-19 vaccines. however, the underlying mechanisms have not been fully elucidated. Here, we investigated antibody responses and explored the response of germinal center (GC) to priming with inactivated vaccines and boosting with heterologous adenoviral-vectored vaccines or homologous inactivated vaccines in mice. Antibody responses were dramatically enhanced by both boosting regimens. Heterologous immunization induced more robust GC activation, characterized by increased Tfh cell populations and enhanced helper function. Additionally, increased B-cell activation and antibody production were observed in a heterologous regimen. Libra-seq was used to compare the differences of S1-, S2- and NTD-specific B cells between homologous and heterologous vaccination, respectively. S2-specific CD19+ B cells presented increased somatic hypermutations (SHMs), which were mainly enriched in plasma cells. Moreover, a heterologous booster dose promoted the clonal expansion of B cells specific to S2 and NTD regions. In conclusion, the functional role of Tfh and B cells following SARS-CoV-2 heterologous vaccination may be important for modulating antibody responses. These findings provide new insights for the development of SARS-CoV-2 vaccines that induce more robust antibody response.
Keywords: Libra-seq; SARS-CoV-2; SHM; Tfh cells; germinal center; heterologous; homologous.