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Novel mRNA vaccines for SARS-CoV-2 have been authorized for emergency use. Despite their efficacy in clinical trials, data on mRNA vaccine-induced immune responses are mostly limited to serological analyses. Here, we interrogated antibody and antigen-specific memory B cells over time in 33 SARS-CoV-2 naïve and 11 SARS-CoV-2 recovered subjects. SARS-CoV-2 naïve individuals required both vaccine doses for optimal increases in antibodies, particularly for neutralizing titers against the B.1.351 variant. Memory B cells specific for full-length spike protein and the spike receptor binding domain (RBD) were also efficiently primed by mRNA vaccination and detectable in all SARS-CoV-2 naive subjects after the second vaccine dose, though the memory B cell response declined slightly with age. In SARS-CoV-2 recovered individuals, antibody and memory B cell responses were significantly boosted after the first vaccine dose; however, there was no increase in circulating antibodies, neutralizing titers, or antigen-specific memory B cells after the second dose. This robust boosting after the first vaccine dose strongly correlated with levels of pre-existing memory B cells in recovered individuals, identifying a key role for memory B cells in mounting recall responses to SARS-CoV-2 antigens. Together, our data demonstrated robust serological and cellular priming by mRNA vaccines and revealed distinct responses based on prior SARS-CoV-2 exposure, whereby COVID-19 recovered subjects may only require a single vaccine dose to achieve peak antibody and memory B cell responses. These findings also highlight the utility of defining cellular responses in addition to serologies and may inform SARS-CoV-2 vaccine distribution in a resource-limited setting. Copyright © 2021, American Association for the Advancement of Science.


Rishi R Goel, Sokratis A Apostolidis, Mark M Painter, Divij Mathew, Ajinkya Pattekar, Oliva Kuthuru, Sigrid Gouma, Philip Hicks, Wenzhao Meng, Aaron M Rosenfeld, Sarah Dysinger, Kendall A Lundgreen, Leticia Kuri-Cervantes, Sharon Adamski, Amanda Hicks, Scott Korte, Derek A Oldridge, Amy E Baxter, Josephine R Giles, Madison E Weirick, Christopher M McAllister, Jeanette Dougherty, Sherea Long, Kurt D'Andrea, Jacob T Hamilton, Michael R Betts, Eline T Luning Prak, Paul Bates, Scott E Hensley, Allison R Greenplate, E John Wherry. Distinct antibody and memory B cell responses in SARS-CoV-2 naïve and recovered individuals following mRNA vaccination. Science immunology. 2021 Apr 15;6(58)

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PMID: 33858945

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