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Memory CD8+ T cell diversity and B cell responses correlate with protection against SARS-CoV-2 following mRNA vaccination

2022; Nature Portfolio; Volume: 23; Issue: 10 Linguagem: Inglês

10.1038/s41590-022-01313-z

1529-2916

Nadia Brasu, Ines Elia, Valentina Russo, Gaia Montacchiesi, Simona Aversano Stabile, Carlo De Intinis, Francesco Fesi, Katiuscia Gizzi, Marco Macagno, Monica Montone, Benedetta Mussolin, Alba Grifoni, Silvia Faravelli, Silvia Marchese, Federico Forneris, Raffaele De Francesco, Alessandro Sette, Vincenzo Barnaba, Antonino Sottile, Anna Sapino, Luigia Pace,

vaccines and immunoinformatics approaches

Understanding immune responses to SARS-CoV-2 messenger RNA (mRNA) vaccines is of great interest, principally because of the poor knowledge about the mechanisms of protection. In the present study, we analyzed longitudinally B cell and T cell memory programs against the spike (S) protein derived from ancestral SARS-CoV-2 (Wuhan-1), B.1.351 (beta), B.1.617.2 (delta) and B.1.1.529 (omicron) variants of concern (VOCs) after immunization with an mRNA-based vaccine (Pfizer). According to the magnitude of humoral responses 3 months after the first dose, we identified high and low responders. Opposite to low responders, high responders were characterized by enhanced antibody-neutralizing activity, increased frequency of central memory T cells and durable S-specific CD8+ T cell responses. Reduced binding antibodies titers combined with long-term specific memory T cells that had distinct polyreactive properties were found associated with subsequent breakthrough with VOCs in low responders. These results have important implications for the design of new vaccines and new strategies for booster follow-up. Pace and colleagues assessed the antibody titers, B cell and T cell memory response against SARS-COV-2 in mRNA-vaccinated individuals to show that reduced antibody titers combined with a distinctive memory T cell profile in low vaccine responders correlated with breakthrough infection.