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2021-10-08Zeitschriftenartikel
Cross-reactive CD4+ T cells enhance SARS-CoV-2 immune responses upon infection and vaccination
dc.contributor.authorLoyal, Lucie
dc.contributor.authorBraun, Julian
dc.contributor.authorHenze, Larissa
dc.contributor.authorKruse, Beate
dc.contributor.authorDingeldey, Manuela
dc.contributor.authorReimer, Ulf
dc.contributor.authorKern, Florian
dc.contributor.authorSchwarz, Tatjana
dc.contributor.authorMangold, Maike
dc.contributor.authorUnger, Clara
dc.contributor.authorDörfler, Friederike
dc.contributor.authorKadler, Shirin
dc.contributor.authorRosowski, Jennifer
dc.contributor.authorGürcan, Kübrah
dc.contributor.authorUyar-Aydin, Zehra
dc.contributor.authorFrentsch, Marco
dc.contributor.authorKurth, Florian
dc.contributor.authorSchnatbbaum, Karsten
dc.contributor.authorEckey, Maren
dc.contributor.authorHippenstiel, Stefan
dc.contributor.authorHocke, Andreas
dc.contributor.authorMüller, Marcel A.
dc.contributor.authorSawitzki, Birgit
dc.contributor.authorMiltenyi, Stefan
dc.contributor.authorPaul, Friedemann
dc.contributor.authorMall, Marcus A.
dc.contributor.authorWenschuh, Holger
dc.contributor.authorVoigt, Sebastian
dc.contributor.authorDrosten, Christian
dc.contributor.authorLauster, Roland
dc.contributor.authorLachman, Nils
dc.contributor.authorSander, Leif-Erik
dc.contributor.authorCorman, Victor M.
dc.contributor.authorRöhmel, Jobst
dc.contributor.authorMeyer-Arndt, Lil
dc.contributor.authorThiel, Andreas
dc.contributor.authorGiesecke-Thiel, Claudia
dc.date.accessioned2024-07-10T12:15:27Z
dc.date.available2024-07-10T12:15:27Z
dc.date.issued2021-10-08none
dc.identifier.other10.1126/science.abh1823
dc.identifier.urihttp://edoc.rki.de/176904/11782
dc.description.abstractINTRODUCTION The clinical manifestations of COVID-19 vary from asymptomatic infection to respiratory failure. Severe disease courses are primarily associated with advanced age, immune dysfunctions, and comorbidities. Initially, severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) was thought to encounter an immunologically unprotected population. However, SARS-CoV-2 has significant homologies with endemic seasonal cold coronaviruses (HCoVs), and recent HCoV infection is associated with a less severe course of COVID-19, suggesting a protective role of cross-reactive immunity. RATIONALE The preexistence of SARS-CoV-2–cross-reactive CD4+ T cells in unexposed individuals has been repeatedly demonstrated, but their contribution to host responses is an active area of investigation. Here, we investigated the functional role of preexisting SARS-CoV-2–cross-reactive and HCoV-reactive CD4+ T cells with high resolution. RESULTS We demonstrate broad CD4+ T cell cross-reactivity in unexposed individuals, with the spike glycoprotein serving as one of the immunodominant targets. Although the N-terminal part of spike (covered by the S-I peptide pool) did not elicit cross-reactive T cell responses, the more HCoV-homologous C-terminal section (covered by the S-II peptide pool) induced T cell responses in unexposed donors. We identified a universal immunodominant coronavirus peptide located within the fusion peptide domain of spike (S816-830) recognized by CD4+ T cells in 20% of unexposed individuals, 50 to 60% of SARS-CoV-2 convalescents, and 97% of BNT162b2-vaccinated individuals. S816-830– and spike–cross-reactive T cells were recruited in immune responses to SARS-CoV-2 infection and BNT162b2 COVID-19 mRNA vaccination. S816-830-reactive T cells initially contributed up to 100% of the S-II–reactive CD4+ T cells but their proportion decreased during the course of the S-II–specific immune response. Upon primary vaccination, cross-reactive cellular and humoral immunity exhibited kinetics typical for secondary immune responses. The frequencies of preexisting cross-reactive T cells correlated positively with functional avidity of the T cell receptor, as well as with the induction and stabilization of anti–SARS-CoV-2-S1-IgG and neutralizing antibodies. Although HCoV-responsive T cells are ubiquitous, their frequencies and the frequencies of SARS-CoV-2–cross-reactive CD4+ T cells decreased with age, consistent with an increased vulnerability of the elderly to severe COVID-19 disease. CONCLUSION Preexisting cross-reactive CD4+ T cells enhance immune responses in SARS-CoV-2 infection and BNT162b2 vaccination. Because these cells are greatly diminished in the elderly, our results suggest that their decrease may contribute to the increased susceptibility of this population to severe COVID-19. Preexisting cross-reactive immunity may be responsible for the unexpectedly rapid induction of protective immunity after primary SARS-CoV-2 immunization and the high rate of asymptomatic and mild COVID-19 disease courses.eng
dc.language.isoengnone
dc.publisherRobert Koch-Institut
dc.rights(CC BY 3.0 DE) Namensnennung 3.0 Deutschlandger
dc.rights.urihttp://creativecommons.org/licenses/by/3.0/de/
dc.subject.ddc610 Medizin und Gesundheitnone
dc.titleCross-reactive CD4+ T cells enhance SARS-CoV-2 immune responses upon infection and vaccinationnone
dc.typearticle
dc.identifier.urnurn:nbn:de:0257-176904/11782-7
dc.type.versionpublishedVersionnone
local.edoc.container-titleSciencenone
local.edoc.container-issn1095-9203none
local.edoc.pages12none
local.edoc.type-nameZeitschriftenartikel
local.edoc.container-typeperiodical
local.edoc.container-type-nameZeitschrift
local.edoc.container-urlhttps://www.science.org/journal/sciencenone
local.edoc.container-publisher-nameAmerican Association for the Advancement of Aciende (AAAS)none
local.edoc.container-volume374none
local.edoc.container-issue6564none
local.edoc.container-reportyear2021none
dc.description.versionPeer Reviewednone

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