Pre-vaccination and early B cell signatures predict antibody response to SARS-CoV-2 mRNA vaccine

  1. Lela Kardava
  2. Nicholas Rachmaninoff
  3. William W. Lau
  4. Clarisa M. Buckner
  5. Krittin Trihemasava
  6. Felipe Lopes de Assis
  7. Wei Wang
  8. Xiaozhen Zhang
  9. Yimeng Wang
  10. Chi-I Chiang
  11. Sandeep Narpala
  12. Robert Reger
  13. Genevieve E. McCormack
  14. Catherine A. Seamon
  15. Richard W. Childs
  16. Anthony F. Suffredini
  17. Jeffrey R. Strich
  18. Daniel S. Chertow
  19. Richard T. Davey
  20. Michael C. Sneller
  21. Sarah O’Connell
  22. Yuxing Li
  23. Adrian McDermott
  24. Tae-Wook Chun
  25. Anthony S. Fauci
  26. John S. Tsang
  27. Susan Moir
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Abstract

SARS-CoV-2 mRNA vaccines are highly effective, although weak antibody responses are seen in some individuals with correlates of immunity that remain poorly understood. Here we longitudinally dissected antibody, plasmablast, and memory B cell (MBC) responses to the two-dose Moderna mRNA vaccine in SARS-CoV-2-uninfected adults. Robust, coordinated IgA and IgG antibody responses were preceded by bursts of spike-specific plasmablasts after both doses, but earlier and more intensely after dose two. Distinct antigen-specific MBC populations also emerged post-vaccination with varying kinetics. We identified antigen non-specific pre-vaccination MBC and post-vaccination plasmablasts after dose one and their spike-specific counterparts early after dose two that correlated with subsequent antibody levels. These baseline and response signatures can thus provide early indicators of serological efficacy and explain response variability in the population.

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