Longitudinal T- and B-cell recall response after vaccination with Pfizer-BioNTech mRNA vaccine BNT162b2.

Abstract

Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) caused a pandemic that resulted in the death of millions. The Pfizer-BioNTech mRNA vaccine against SARS-CoV-2 (BNT162b2) induced the development of antigen-specific T and B cells, which correlated with protection from disease. However, their ability to mount a true recall response after reactivation was not addressed. We determined the longevity, intensity, and phenotype of the T- and B-cell recall responses after vaccination with BNT162b2. Twelve participants vaccinated with BNT162b2 were included in this study. Six blood samples were collected before administering the primary dose, at 21 days after the primary dose, and at 1, 3, 6, and 9 months after the booster dose. Antigen-specific B and T cells were stimulated ex vivo, and their abundance, longevity, phenotype, and intensity of their recall responses were analyzed. Plasma and supernatant of activated B cells were used to determine the levels, kinetics, and neutralization potential of antigen-specific immunoglobulins. Vaccination with BNT162b2 resulted in the development of long-lasting neutralizing immunoglobulins, as well as antigen-specific memory CD4⁺ T cells that proliferate on reactivation, promote a protective T_H1 response, and induce IgG/IgA class switching in antigen-specific memory B cells, which are primed to secrete neutralizing antibodies on reactivation. Additionally, antigen-specific memory CD8⁺ T cells proliferate on reactivation and upregulate granzyme and perforin to eliminate infected cells. Vaccination with BNT162b2 induces spike-specific memory T and B cells that are reactivated on antigen exposure to mount a recall response that protects from SARS-CoV-2 infection for up to 9 months after immunization.