Early human B cell signatures of the primary antibody response to mRNA vaccination.
Author
Kardava, LelaRachmaninoff, Nicholas
Lau, William W
Buckner, Clarisa M
Trihemasava, Krittin
Blazkova, Jana
Lopes de Assis, Felipe
Wang, Wei
Zhang, Xiaozhen
Wang, Yimeng
Chiang, Chi-I
Narpala, Sandeep
McCormack, Genevieve E
Liu, Can
Seamon, Catherine A
Sneller, Michael C
O'Connell, Sarah
Li, Yuxing
McDermott, Adrian B
Chun, Tae-Wook
Fauci, Anthony S
Tsang, John S
Moir, Susan
Date
2022-06-27Journal
Proceedings of the National Academy of Sciences of the United States of AmericaPublisher
National Academy of Sciences of the United States of AmericaType
Article
Metadata
Show full item recordAbstract
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.Identifier to cite or link to this item
http://hdl.handle.net/10713/19330ae974a485f413a2113503eed53cd6c53
10.1073/pnas.2204607119
Scopus Count
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