Induction and subsequent decline of S1-specific T cell reactivity after COVID-19 vaccination

Abstract

We analyzed magnitude and duration of SARS-CoV-2-specific T cell responses in healthy, infection-naïve subjects receiving COVID-19 vaccines. Overlapping peptides spanning the N-terminal spike 1 (S1) domain of the spike protein triggered secretion of the T cell-derived cytokine interleukin-2 ex vivo in 94/94 whole blood samples from vaccinated subjects at levels exceeding those recorded in all 45 pre-vaccination samples. S1-specific T cell reactivity was stronger in vaccinated subjects compared with subjects recovering from natural COVID-19 and decayed with an estimated half-life of 134 days in the first six months after the 2nd vaccination. We conclude that COVID-19 vaccination induces robust T cell immunity that subsequently declines. EudraCT 2021-000349-42. https://www.clinicaltrialsregister.eu/ctr-search/search?query=2021-000349-42.

Keywords: COVID-19; Longevity; SARS-CoV-2; T cells; Vaccine.

Fig. 1

Two doses of COVID-19 vaccine trigger robust spike-specific T cell reactivity and antibodies. (A) Spike 1 (S1) peptide-induced formation of IL-2 in plasma supernatants from stimulated whole blood and (B) serum levels of anti-RBD S1 IgG in samples obtained from uninfected, unvaccinated subjects (Ctrl, A: N = 45, B: N = 45), unvaccinated subjects with previously confirmed COVID-19 (Inf, A: N = 8, B: N = 9),) and uninfected subjects after the first (1 dose, A: N = 22, B: N = 30),) or second (2 doses, A: N = 26, B: N = 29),) COVID-19 vaccination. All samples were collected approximately one month (median 28 days, range 18–53 days) after infection or vaccination. Statistics by linear mixed-effects models or t-test.

Fig. 2

Longevity of S1-specific T cell reactivity and S1-IgG after vaccination. (A, 61 samples from 32 individuals) S1 peptide-induced formation of IL-2 in whole blood and (B, 64 samples from 32 individuals) serum levels of anti-RBD S1 IgG in samples obtained from uninfected individuals one, three and six months after receiving their second COVID-19 vaccine dose. Connecting lines indicate samples from the same individual. Estimates of waning of (A) IL-2 and (B) anti-RBD S1 IgG after two vaccine doses are represented by black regression lines generated by linear mixed-effects models. Dotted lines indicate the highest level of S1 peptide-induced IL-2 (A) and the highest anti-RBD S1 IgG (B) in samples from uninfected, unvaccinated subjects. Statistics by linear mixed-effects models.