RT Journal Article
SR Electronic
T1 Efficient recall of Omicron-reactive B cell memory after a third dose of SARS-CoV-2 mRNA vaccine
JF bioRxiv
FD Cold Spring Harbor Laboratory
SP 2022.02.20.481163
DO 10.1101/2022.02.20.481163
A1 Rishi R. Goel
A1 Mark M. Painter
A1 Kendall A. Lundgreen
A1 Sokratis A. Apostolidis
A1 Amy E. Baxter
A1 Josephine R. Giles
A1 Divij Mathew
A1 Ajinkya Pattekar
A1 Arnold Reynaldi
A1 David S. Khoury
A1 Sigrid Gouma
A1 Philip Hicks
A1 Sarah Dysinger
A1 Amanda Hicks
A1 Harsh Sharma
A1 Sarah Herring
A1 Scott Korte
A1 Wumesh KC
A1 Derek A. Oldridge
A1 Rachel I. Erickson
A1 Madison E. Weirick
A1 Christopher M. McAllister
A1 Moses Awofolaju
A1 Nicole Tanenbaum
A1 Jeanette Dougherty
A1 Sherea Long
A1 Kurt D’Andrea
A1 Jacob T. Hamilton
A1 Maura McLaughlin
A1 Justine C. Williams
A1 Sharon Adamski
A1 Oliva Kuthuru
A1 Elizabeth M. Drapeau
A1 Miles P. Davenport
A1 Scott E. Hensley
A1 Paul Bates
A1 Allison R. Greenplate
A1 E. John Wherry
YR 2022
UL http://biorxiv.org/content/early/2022/02/22/2022.02.20.481163.abstract
AB Despite a clear role in protective immunity, the durability and quality of antibody and memory B cell responses induced by mRNA vaccination, particularly by a 3rd dose of vaccine, remains unclear. Here, we examined antibody and memory B cell responses in a cohort of individuals sampled longitudinally for ∼9-10 months after the primary 2-dose mRNA vaccine series, as well as for ∼3 months after a 3rd mRNA vaccine dose. Notably, antibody decay slowed significantly between 6- and 9-months post-primary vaccination, essentially stabilizing at the time of the 3rd dose. Antibody quality also continued to improve for at least 9 months after primary 2-dose vaccination. Spike- and RBD-specific memory B cells were stable through 9 months post-vaccination with no evidence of decline over time, and ∼40-50% of RBD-specific memory B cells were capable of simultaneously recognizing the Alpha, Beta, Delta, and Omicron variants. Omicron-binding memory B cells induced by the first 2 doses of mRNA vaccine were boosted significantly by a 3rd dose and the magnitude of this boosting was similar to memory B cells specific for other variants. Pre-3rd dose memory B cell frequencies correlated with the increase in neutralizing antibody titers after the 3rd dose. In contrast, pre-3rd dose antibody titers inversely correlated with the fold-change of antibody boosting, suggesting that high levels of circulating antibodies may limit reactivation of immunological memory and constrain further antibody boosting by mRNA vaccines. These data provide a deeper understanding of how the quantity and quality of antibody and memory B cell responses change over time and number of antigen exposures. These data also provide insight into potential immune dynamics following recall responses to additional vaccine doses or post-vaccination infections.Competing Interest StatementS.E.H. has received consultancy fees from Sanofi Pasteur, Lumen, Novavax, and Merck for work unrelated to this study. A.R.G. is a consultant for Relation Therapeutics. E.J.W. is consulting for or is an advisor for Merck, Marengo, Janssen, Related Sciences, Synthekine, and Surface Oncology. E.J.W. is a founder of Surface Oncology, Danger Bio, and Arsenal Biosciences. The authors declare no other competing interests.