Research ArticleCORONAVIRUS

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

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Science Immunology  15 Apr 2021:
Vol. 6, Issue 58, eabi6950
DOI: 10.1126/sciimmunol.abi6950

B cell memory after SARS-CoV-2 mRNA vaccination

Clinical trials of mRNA-based vaccines for SARS-CoV-2 have confirmed their ability to provide robust protection against COVID-19. Many studies demonstrate antibody responses to these vaccines, but the timing of B cell memory formation after vaccination is unclear. Goel et al. studied the antibody and B cell memory responses to SARS-CoV-2 mRNA vaccines using a cohort of SARS-CoV-2 naïve and convalescent patients that received the Pfizer or Moderna vaccines. Two shots of the mRNA vaccines were needed to induce peak antibody and memory B cell responses against SARS-CoV-2 in naïve patients, whereas only one shot induced peak responses in convalescent patients. These antibodies could neutralize the more infectious B.1.351 variant. These data provide further evidence of robust, protective immune responses to SARS-CoV-2 after mRNA vaccination.


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 naïve subjects after the second vaccine dose, although 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 preexisting 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.

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