Abstract
Vaccination against severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) is effective in preventing hospitalization from severe COVID-19. However, multiple reports of breakthrough infections and of waning antibody titers have raised concerns on the durability of the vaccine, and current vaccination strategies now propose administration of a third dose. Here, we monitored T cell responses to the Spike protein of SARS-CoV-2 in 71 healthy donors vaccinated with two doses of the Pfizer-BioNTech mRNA vaccine (BNT162b2) for up to 6 months after vaccination. We found that vaccination induced the development of a sustained anti-viral CD4+ and CD8+ T cell response. These cells appeared before the development of high antibody titers, displayed markers of immunological maturity and stem cell memory, survived the physiological contraction of the immune response, and persisted for at least 6 months. Collectively, these data show that vaccination with BNT162b2 elicits an immunologically competent and long-lived SARS-CoV-2–specific T cell population.
Highlights
Half of the world population has developed some immunity to SARS-CoV-2, either through natural infection or through vaccination [1] but it is unclear if this immunity will last longterm
All individuals in our cohort were devoid of anti-Receptor-Binding Domain (RBD) antibodies at baseline, and significant levels appeared in 100% of individuals only after the second dose (Fig. S1A), (T1: median 28; T2: median 1786; T3: median 517)
The data show that BNT162b2 induces the production of anti-RBD antibodies which decrease over time but are maintained at high levels for at least 6 months
Summary
Half of the world population has developed some immunity to SARS-CoV-2, either through natural infection or through vaccination [1] but it is unclear if this immunity will last longterm. Initial in vitro studies characterized patient-derived antigen-specific CD4+ and CD8+ lymphocytes reactive with overlapping peptide pools from the SARS-CoV-2 Spike protein [3, 5, 23, 25], showing the establishment of an effective anti-viral response after natural infection. Spike-specific T cells persist in COVID-19 convalescents [2, 26,27,28], arise following vaccination with mRNA-based SARS-CoV-2 vaccines, and include specialized subsets which can both sustain cytotoxic functions and participate to the maturation of antibodyproducing B cells in lymph node germinal centers [11, 15,16,17, 29, 30]. Subjects with undetectable or impaired humoral responses can recover from COVID-19 [31,32,33], underlining the importance of cellular immunity in clearing SARS-
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