期刊名称：Proceedings of the National Academy of Sciences
印刷版ISSN：0027-8424
电子版ISSN：1091-6490
出版年度：2022
卷号：119
期号：28
DOI：10.1073/pnas.2204607119
语种：English
出版社：The National Academy of Sciences of the United States of America
摘要：Significance
The pandemic caused by severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) accelerated development of messenger RNA (mRNA) vaccines, which have proven to be highly effective against COVID-19. However, antibody responses vary widely and wane over time. This study evaluated the range and kinetics of the primary antibody response to SARS-CoV-2 mRNA-based vaccination in parallel with the B cells that are involved in generating and maintaining this response. These include plasmablasts, the antibody-secreting cells that arise rapidly yet transiently following immunization, and memory B cells, a heterogeneous population that can provide long-lasting immunity. Our results show that the antibody response was tightly linked to early plasmablasts, while the cellular response was sustained by a distinct population of memory B cells.
Messenger RNA (mRNA) vaccines against severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) are highly effective at inducing protective immunity. However, weak antibody responses are seen in some individuals, and cellular correlates of immunity remain poorly defined, especially for B cells. Here we used unbiased approaches to longitudinally dissect primary antibody, plasmablast, and memory B cell (MBC) responses to the two-dose mRNA-1273 vaccine in SARS-CoV-2–naive adults. Coordinated immunoglobulin A (IgA) and IgG antibody responses were preceded by bursts of spike-specific plasmablasts after both doses but earlier and more intensely after dose 2. While antibody and B cell cellular responses were generally robust, they also varied within the cohort and decreased over time after a dose-2 peak. Both antigen-nonspecific postvaccination plasmablast frequency after dose 1 and their spike-specific counterparts early after dose 2 correlated with subsequent antibody levels. This correlation between early plasmablasts and antibodies remained for titers measured at 6 months after vaccination. Several distinct antigen-specific MBC populations emerged postvaccination with varying kinetics, including two MBC populations that correlated with 2- and 6-month antibody titers. Both were IgG-expressing MBCs: one less mature, appearing as a correlate after the first dose, while the other MBC correlate showed a more mature and resting phenotype, emerging as a correlate later after dose 2. This latter MBC was also a major contributor to the sustained spike-specific MBC response observed at month 6. Thus, these plasmablasts and MBCs that emerged after both the first and second doses with distinct kinetics are potential determinants of the magnitude and durability of antibodies in response to mRNA-based vaccination.
