Comparison of antigen-specific B cell responses reveals disparity in immunogenicity and memory B cell formation across COVID-19 vaccine platforms
Chang Ming Guo, Xin Chai, Maidaiti Baerlike, Yingping Liu, Yao Wang, Fei Shao, Qingrui Huang, Weiguo Zhang, Shan Cen, Yijie Dong, Yunlong Cao, Jinghua Yan, Xuyu Zhou, Zhaolin Hua, Baidong Hou
Abstract
Various vaccine technologies have been employed in the coronavirus disease 2019 (COVID-19) vaccines, including whole inactivated virus (WIV), recombinant protein, mRNA, and nanoparticle vaccines. To elucidate the cellular mechanisms underlying the immune responses elicited by different vaccines, we examined and compared antigen-specific B cell responses targeting the receptor-binding domain (RBD) of the viral spike protein. We found that the nanoparticle vaccine pathogen-like antigens-RBD (PLA-RBD) and the mRNA vaccine demonstrated superior immunogenicity compared with the WIV vaccine and the RBD-dimer, a recombinant protein vaccine. Interestingly, the WIV vaccine contains toll-like receptor ligands that enhance IgG2a/c class-switching. For the mRNA vaccine, although it induces robust germinal center responses and T follicular helper (Tfh) cells, it has limited ability to induce memory B cells and long-lived plasma cells. These results indicate that vaccine formats significantly influence both the quantity and quality of immune responses, providing valuable insights for the future development of vaccines. • Examining the severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2)-specific B cell response allows for a comparison of vaccines in various formats. • The nanoparticle and mRNA vaccines exhibit superior immunogenicity compared with inactivated and recombinant protein vaccines. • Despite inducing a robust germinal center response, the mRNA vaccine elicits a limited number of memory B cells.