T cell responses induced by SARS-CoV-2 mRNA vaccination are associated with clonal replacement

mRNA vaccines against the Spike glycoprotein of severe acute respiratory syndrome type 2 coronavirus (SARS-CoV-2) elicit strong T-cell responses. However, it is unknown whether T cell clones induced by the first vaccination or newly generated T cell clones dominate responses to the secondary vaccination. Here, we analyzed the kinetic profile of Spike-reactive T-cell clones before the first dose, one week after the first and second dose, and four weeks after the second dose of the BNT162b mRNA vaccine. Interestingly, a new set of Spike-reactive CD8+ T cell clones exhibited the greatest expansion following secondary vaccination and replaced the clones that had responded to the primary vaccination. Single-cell mRNA/protein/TCR analysis revealed that the first-responder clones exhibited a terminally differentiated phenotype, whereas second-responder clones exhibited an actively proliferating phenotype. These results show that Spike-reactive T cell responses induced by repetitive mRNA vaccination are augmented and maintained by replacement with newly-generated clones with proliferative potential. One Sentence SummaryTCR repertoire analysis following mRNA vaccination against SARS-CoV-2 revealed the replacement of Spike-reactive T cell clones.

Transition of antibody titers after the SARS-CoV-2 mRNA vaccine in Japanese healthcare workers

Since February 2021, health care workers in Japan have been preferentially vaccinated with a messenger RNA vaccine (BNT162b2/Pfizer) against severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2). While many studies have confirmed that this vaccine is highly effective in reducing hospitalizations and deaths from coronavirus disease 2019 (COVID-19), antibody titers tend to decline at 3 months, leading to a risk of breakthrough infections. Thus, information is needed to support decision making regarding the third vaccination. In this study, we investigated transition of the anti-SARS-CoV-2 receptor-binding domain (RBD) IgG and neutralizing antibody titers of 41 vaccinated Japanese healthcare workers. Samples were collected seven times starting 1 week before vaccination until 6 months post-vaccination. Anti-SARS-CoV-2 RBD IgG levels peaked at 7 days after the booster, then declined over time and decreased to <10% at 6 months after the booster. Workers with low anti-SARS-CoV-2 RBD IgG levels also had low neutralizing antibody titers. These data support the active use of boosters for healthcare workers, especially for those with low anti-SARS-CoV-2 RBD IgG levels.