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    Early human B cell signatures of the primary antibody response to mRNA vaccination.

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    Author
    Kardava, Lela
    Rachmaninoff, 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
    Show allShow less

    Date
    2022-06-27
    Journal
    Proceedings of the National Academy of Sciences of the United States of America
    Publisher
    National Academy of Sciences of the United States of America
    Type
    Article
    
    Metadata
    Show full item record
    See at
    https://doi.org/10.1073/pnas.2204607119
    Abstract
    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.
    Keyword
    B cells
    SARS-CoV-2
    adaptive immunity
    antibodies
    mRNA vaccines
    Identifier to cite or link to this item
    http://hdl.handle.net/10713/19330
    ae974a485f413a2113503eed53cd6c53
    10.1073/pnas.2204607119
    Scopus Count
    Collections
    UMB Coronavirus Publications
    UMB Open Access Articles

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