The functional relevance of pre-existing cross-immunity to SARS-CoV-2 is a subject of intense debate. Here, we show that human endemic coronavirus (HCoV)-reactive and SARS-CoV-2-cross-reactive CD4(+) T cells are ubiquitous but decrease with age. We identified a universal immunodominant coronavirus-specific spike peptide (S816-830) and demonstrate that pre-existing spike- and S816-830-reactive T cells were recruited into immune responses to SARS-CoV-2 infection and their frequency correlated with anti-SARS-CoV-2-S1-IgG antibodies. Spike-cross-reactive T cells were also activated after primary BNT162b2 COVID-19 mRNA vaccination displaying kinetics similar to secondary immune responses. Our results highlight the functional contribution of pre-existing spike-cross-reactive T cells in SARS-CoV-2 infection and vaccination. Cross-reactive immunity may account for the unexpectedly rapid induction of immunity following primary SARS-CoV-2 immunization and the high rate of asymptomatic/mild COVID-19 disease courses.
- Loyal, L.
- Braun, J.
- Henze, L.
- Kruse, B.
- Dingeldey, M.
- Reimer, U.
- Kern, F.
- Schwarz, T.
- Mangold, M.
- Unger, C.
- Dörfler, F.
- Kadler, S.
- Rosowski, J.
- Gürcan, K.
- Uyar-Aydin, Z.
- Frentsch, M.
- Kurth, F.
- Schnatbaum, K.
- Eckey, M.
- Hippenstiel, S.
- Hocke, A.
- Müller, M. A.
- Sawitzki, B.
- Miltenyi, S.
- Paul, F.
- Mall, M. A.
- Wenschuh, H.
- Voigt, S.
- Drosten, C.
- Lauster, R.
- Lachman, N.
- Sander, L. E.
- Corman, V. M.
- Röhmel, J.
- Meyer-Arndt, L.
- Thiel, A.
- Giesecke-Thiel, C.
