Cross-reactive CD4 + T cells enhance SARS-CoV-2 immune responses upon infection and vaccination

• Published in: Science (American Association for the Advancement of Science) Vol. 374; no. 6564; p. eabh1823
• Main Authors: Loyal, Lucie, Braun, Julian, Henze, Larissa, Kruse, Beate, Dingeldey, Manuela, Reimer, Ulf, Kern, Florian, Schwarz, Tatjana, Mangold, Maike, Unger, Clara, Dörfler, Friederike, Kadler, Shirin, Rosowski, Jennifer, Gürcan, Kübrah, Uyar-Aydin, Zehra, Frentsch, Marco, Kurth, Florian, Schnatbaum, Karsten, Eckey, Maren, Hippenstiel, Stefan, Hocke, Andreas, Müller, Marcel A., Sawitzki, Birgit, Miltenyi, Stefan, Paul, Friedemann, Mall, Marcus A., Wenschuh, Holger, Voigt, Sebastian, Drosten, Christian, Lauster, Roland, Lachman, Nils, Sander, Leif-Erik, Corman, Victor M., Röhmel, Jobst, Meyer-Arndt, Lil, Thiel, Andreas, Giesecke-Thiel, Claudia
• Format: Journal Article
• Language: English
• Published: United States The American Association for the Advancement of Science 08.10.2021
• Subjects: Adult; Age; Age Factors; Aged; Aged, 80 and over; Antibodies; Asymptomatic; Asymptomatic Diseases; Asymptomatic infection; Avidity; BNT162 Vaccine; CD3 Complex - immunology; CD4 antigen; CD4-Positive T-Lymphocytes - immunology; Coronaviridae; Coronaviruses; COVID-19; COVID-19 - immunology; COVID-19 vaccines; COVID-19 Vaccines - immunology; Cross Reactions; Cross-protection; Cross-reactivity; Female; Glycoproteins; Homology; Humans; Humoral immunity; Immune response; Immune system; Immunity; Immunization; Immunodominant Epitopes - immunology; Immunoglobulin G; Immunological memory; Immunology; Infections; Kinetics; Logical Thinking; Lymphocytes; Lymphocytes T; Male; Memory cells; Middle Aged; mRNA; Older people; Open Reading Frames; Peptide Fragments - immunology; Peptides; Respiratory diseases; Respiratory failure; SARS-CoV-2 - genetics; SARS-CoV-2 - immunology; Severe acute respiratory syndrome coronavirus 2; Spike glycoprotein; Spike Glycoprotein, Coronavirus - immunology; Spike protein; T cell receptors; Vaccination; Vaccines; Viral diseases; Young Adult
• ISSN: 0036-8075; 1095-9203; 1095-9203
• DOI: 10.1126/science.abh1823

There is mounting evidence that immunological memory after infection with seasonal human coronaviruses (hCoVs) contributes to cross-protection against severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2). Loyal et al . identified a universal immunodominant coronavirus peptide found within the fusion peptide domain of coronavirus spike protein. This peptide is recognized by CD4 + T cells in 20% of unexposed individuals, more than 50% of SARS-CoV-2 convalescents, and 97% of subjects treated with the Pfizer–BioNTech COVID-19 vaccine. Although ubiquitous, these coronavirus-reactive T cells decreased with age, which may explain in part the increased susceptibility of elderly people to COVID-19. —STS Preexisting spike–cross-reactive T cells correlate with higher neutralizing anti-spike protein antibodies in SARS-CoV-2 infection and vaccination The functional relevance of preexisting cross-immunity to severe acute respiratory syndrome coronavirus 2 (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 preexisting 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 messenger RNA vaccination and displayed kinetics similar to those of secondary immune responses. Our results highlight the functional contribution of preexisting spike–cross-reactive T cells in SARS-CoV-2 infection and vaccination. Cross-reactive immunity may account for the unexpectedly rapid induction of immunity after primary SARS-CoV-2 immunization and the high rate of asymptomatic or mild COVID-19 disease courses.