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bioRxiv · 10.1101/2022.02.20.481163

Efficient recall of Omicron-reactive B cell memory after a third dose of SARS-CoV-2 mRNA vaccine

Goel, R. R.·Painter, M. M.·Lundgreen, K. A.·Apostolidis, S. A.·Baxter, A. E.·Giles, J. R.·Mathew, D.·Pattekar, A.·Reynaldi, A.·Khoury, D. S.·Gouma, S.·Hicks, P.·Dysinger, S.·Hicks, A.·Sharma, H.·Herring, S.·Korte, S.·KC, W.·Oldridge, D. A.·Erickson, R. I.·Weirick, M. E.·McAllister, C. M.·Awofolaju, M.·Tanenbaum, N.·Dougherty, J.·Long, S.·D'Andrea, K.·Hamilton, J. T.·McLaughlin, M.·Williams, J. C.·Adamski, S.·Kuthuru, O.·Drapeau, E. M.·Davenport, M. P.·Hensley, S. E.·Bates, P.·Greenplate, A. R.·Wherry, E. J.
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Abstract

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. Graphical Summary O_FIG O_LINKSMALLFIG WIDTH=200 HEIGHT=123 SRC="FIGDIR/small/481163v1_ufig1.gif" ALT="Figure 1"> View larger version (20K): org.highwire.dtl.DTLVardef@123d2d9org.highwire.dtl.DTLVardef@e7db82org.highwire.dtl.DTLVardef@1fc73deorg.highwire.dtl.DTLVardef@11b21f9_HPS_FORMAT_FIGEXP M_FIG C_FIG

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Goel, R. R., Painter, M. M., Lundgreen, K. A., Apostolidis, S. A., Baxter, A. E., Giles, J. R., Mathew, D., Pattekar, A., Reynaldi, A., Khoury, D. S., Gouma, S., Hicks, P., Dysinger, S., Hicks, A., Sharma, H., Herring, S., Korte, S., KC, W., Oldridge, D. A., Erickson, R. I., Weirick, M. E., McAllister, C. M., Awofolaju, M., Tanenbaum, N., Dougherty, J., Long, S., D'Andrea, K., Hamilton, J. T., McLaughlin, M., Williams, J. C., Adamski, S., Kuthuru, O., Drapeau, E. M., Davenport, M. P., Hensley, S. E., Bates, P., Greenplate, A. R., Wherry, E. J.. 2022-02-22. Efficient recall of Omicron-reactive B cell memory after a third dose of SARS-CoV-2 mRNA vaccine. https://doi.org/10.1101/2022.02.20.481163

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