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Front Immunol . mRNA-based SARS-CoV-2 Comirnaty vaccine elicits weak and short specific memory B cell response in individuals with no previous infec

tetano

Editor, Senior Moderator
Front Immunol


. 2023 Jun 29;14:1127379.
doi: 10.3389/fimmu.2023.1127379. eCollection 2023. mRNA-based SARS-CoV-2 Comirnaty vaccine elicits weak and short specific memory B cell response in individuals with no previous infection

José L Casado[SUP] 1 2 [/SUP], Pilar Vizcarra[SUP] 1 2 [/SUP], Adrián Martín-Hondarza[SUP] 3 [/SUP], Sandra Gómez-Maldonado[SUP] 1 [/SUP], Magdalena Muedra-Sánchez[SUP] 4 [/SUP], Judith Del Pino[SUP] 1 [/SUP], Itria G Mirabella[SUP] 4 [/SUP], Sara Martín-Colmenarejo[SUP] 1 [/SUP], Johannes Haemmerle[SUP] 4 [/SUP], Marina Fernández-Escribano[SUP] 4 [/SUP], Alejandro Vallejo[SUP] 1 2 3 [/SUP]



Affiliations
Free PMC article Abstract

Objectives: The dynamics of the memory B cell (MBC) repertoire after SARS-CoV-2 vaccination is crucial for assessing long-term immunity. We compare spike-specific MBC responses between SARS-CoV-2 unexposed and recovered individuals, and their impact on breakthrough infections during follow-up.
Methods: Spike-specific MBC and T cells were quantified at inclusion and after two doses of mRNA vaccine in a longitudinal cohort of 85 naïve and 64 recovered participants (47 with positive serology and 17 with negative serology after infection).
Results: At inclusion, there was minimal spike-specific MBC in naïve SARS-CoV-2 individuals. After the second vaccine dose, MBCs were significantly boosted in naïve individuals, but reached a significantly lower level than that observed even in unvaccinated SARS-CoV-2 convalescents (p<0.001). Furthermore, while the secondary memory B cell (MBC) population consisted of 100%, 33%, and 76% IgG[SUP]+[/SUP], IgM[SUP]+[/SUP], and IgA[SUP]+[/SUP] expressing cells, respectively, in the unexposed group, the MBC response showed a significant decrease across all isotypes. Similarly, although secondary specific IgG[SUP]+[/SUP], IgM[SUP]+[/SUP], and IgA[SUP]+[/SUP]-MBC isotypes were found in 100%, 39%, and 76% of the unexposed participants, respectively, the magnitude of the MBC levels was significantly lower for all the isotypes compared to convalescents. Interestingly, convalescents without an initial serological response had a lower MBC response, like what found in unexposed subjects. There was an inverse correlation between specific MBCs (r=-0.307; p=0.027), especially for isotype IgA[SUP]+[/SUP] (r=-0.279, p=0.045), and the time since the second vaccination dose. Furthermore, during a median follow-up of 434 days (IQR, 339-495), 49 out of 149 individuals (33%) became infected, 29 in naïve and 20 in convalescent individuals, showing a significant correlation between spike-specific MBC magnitude after vaccination and the time for SARS-CoV-2 infection, especially for IgA[SUP]+[/SUP]/IgG[SUP]+[/SUP] MBC isotypes.
Conclusions: MBCs were primed by mRNA-based vaccination in most cases, but SARS-CoV-2 naïve individuals had a blunted specific MBC response, and this was associated with a shorter time to breakthrough SARS-CoV-2 infection.

Keywords: B cell response; COVID-19; SARS-CoV-2; convalescents; longterm immunity.

 
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