Early human B cell signatures of the primary antibody response to mRNA vaccination.
Lau, William W
Buckner, Clarisa M
Lopes de Assis, Felipe
McCormack, Genevieve E
Seamon, Catherine A
Sneller, Michael C
McDermott, Adrian B
Fauci, Anthony S
Tsang, John S
JournalProceedings of the National Academy of Sciences of the United States of America
PublisherNational Academy of Sciences of the United States of America
MetadataShow full item record
AbstractMessenger 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 itemhttp://hdl.handle.net/10713/19330
- Pre-vaccination and early B cell signatures predict antibody response to SARS-CoV-2 mRNA vaccine.
- Authors: Kardava L, Rachmaninoff N, Lau WW, Buckner CM, Trihemasava K, de Assis FL, Wang W, Zhang X, Wang Y, Chiang CI, Narpala S, Reger R, McCormack GE, Seamon CA, Childs RW, Suffredini AF, Strich JR, Chertow DS, Davey RT, Sneller MC, Oâ Connell S, Li Y, McDermott A, Chun TW, Fauci AS, Tsang JS, Moir S
- Issue date: 2021 Jul 7
- Determinants of early antibody responses to COVID-19 mRNA vaccines in a cohort of exposed and naïve healthcare workers.
- Authors: Moncunill G, Aguilar R, Ribes M, Ortega N, Rubio R, Salmerón G, Molina MJ, Vidal M, Barrios D, Mitchell RA, Jiménez A, Castellana C, Hernández-Luis P, Rodó P, Méndez S, Llupià A, Puyol L, Rodrigo Melero N, Carolis C, Mayor A, Izquierdo L, Varela P, Trilla A, Vilella A, Barroso S, Angulo A, Engel P, Tortajada M, García-Basteiro AL, Dobaño C
- Issue date: 2022 Jan
- Immunogenicity and tolerability of COVID-19 messenger RNA vaccines in primary immunodeficiency patients with functional B-cell defects.
- Authors: Pham MN, Murugesan K, Banaei N, Pinsky BA, Tang M, Hoyte E, Lewis DB, Gernez Y
- Issue date: 2022 Mar
- Kinetics of the Antibody Response to Boostering With Three Different Vaccines Against SARS-CoV-2.
- Authors: Markewitz R, Juhl D, Pauli D, Görg S, Junker R, Rupp J, Engel S, Steinhagen K, Herbst V, Zapf D, Krüger C, Brockmann C, Leypoldt F, Dargvainiene J, Schomburg B, Sharifzadeh S, Nejad LS, Wandinger KP, Ziemann M
- Issue date: 2022
- Seroresponse to SARS-CoV-2 Vaccines among Maintenance Dialysis Patients over 6 Months.
- Authors: Hsu CM, Weiner DE, Manley HJ, Aweh GN, Ladik V, Frament J, Miskulin D, Argyropoulos C, Abreo K, Chin A, Gladish R, Salman L, Johnson D, Lacson EK Jr
- Issue date: 2022 Mar