Distinct antibody and memory B cell responses in SARS-CoV-2 naïve and recovered individuals following mRNA vaccination

Goel, Rishi R.; Apostolidis, Sokratis A.; Painter, Mark M.; Mathew, Divij; Pattekar, Ajinkya; Kuthuru, Oliva; Gouma, Sigrid; Hicks, Philip; Meng, Wenzhao; Rosenfeld, Aaron M.; Dysinger, Sarah; Lundgreen, Kendall A.; Kuri-Cervantes, Leticia; Adamski, Sharon; Hicks, Amanda; Korte, Scott; Oldridge, Derek A.; Baxter, Amy E.; Giles, Josephine R.; Weirick, Madison E.; McAllister, Christopher M.; Dougherty, Jeanette; Long, Sherea; D’Andrea, Kurt; Hamilton, Jacob T.; Betts, Michael R.; Luning Prak, Eline T.; Bates, Paul; Hensley, Scott E.; Greenplate, Allison R.; Wherry, E. John

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.