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

ABSTRACT: 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.

SUBMITTER: Loyal L

PROVIDER: S-EPMC10026850 | biostudies-literature | 2021 Oct

REPOSITORIES: biostudies-literature

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Cross-reactive CD4<sup>+</sup> T cells enhance SARS-CoV-2 immune responses upon infection and vaccination.

Loyal Lucie L Braun Julian J Henze Larissa L Kruse Beate B Dingeldey Manuela M Reimer Ulf U Kern Florian F Schwarz Tatjana T Mangold Maike M Unger Clara C Dörfler Friederike F Kadler Shirin S Rosowski Jennifer J Gürcan Kübrah K Uyar-Aydin Zehra Z Frentsch Marco M Kurth Florian F Schnatbaum Karsten K Eckey Maren M Hippenstiel Stefan S Hocke Andreas A Müller Marcel A MA Sawitzki Birgit B Miltenyi Stefan S Paul Friedemann F Mall Marcus A MA Wenschuh Holger H Voigt Sebastian S Drosten Christian C Lauster Roland R Lachman Nils N Sander Leif-Erik LE Corman Victor M VM Röhmel Jobst J Meyer-Arndt Lil L Thiel Andreas A Giesecke-Thiel Claudia C

Science (New York, N.Y.) 20211008 6564

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<sup>+</sup> 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 ...[more]

PMID: 34465633

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Project description:ImportanceIn the ongoing COVID-19 pandemic, there remain unanswered questions regarding the nature and importance of the humoral immune response against other coronaviruses. Although coinfection of the Middle East respiratory syndrome coronavirus (MERS-CoV) with the SARS-CoV-2 has not been documented yet, several patients previously infected with MERS-CoV received the COVID-19 vaccine; data describing how preexisting MERS-CoV immunity may shape the response to SARS-CoV-2 following infection or vaccination are lacking.ObjectiveTo characterize the cross-reactive and protective humoral responses in patients exposed to both MERS-CoV infection and SARS-CoV-2 vaccination.Design, setting, and participantsThis cohort study involved a total of 18 sera samples collected from 14 patients with MERS-CoV infection before (n = 12) and after (n = 6) vaccination with 2 doses of COVID-19 mRNA vaccine (BNT162b2 or mRNA-1273). Of those patients, 4 had prevaccination and postvaccination samples. Antibody responses to SARS-CoV-2 and MERS-CoV were assessed as well as cross-reactive responses to other human coronaviruses.Main outcomes and measuresThe main outcomes measured were binding antibody responses, neutralizing antibodies, and antibody-dependent cellular cytotoxicity (ADCC) activity. Binding antibodies targeting SARS-CoV-2 main antigens (spike [S], nucleocapsid, and receptor-binding domain) were detected using automated immunoassays. Cross-reactive antibodies with the S1 protein of SARS-CoV, MERS-CoV, and common human coronaviruses were analyzed using a bead-based assay. Neutralizing antibodies (NAbs) against MERS-CoV and SARS-CoV-2 as well as ADCC activity against SARS-CoV-2 were assessed.ResultsA total of 18 samples were collected from 14 male patients with MERS-CoV infection (mean [SD] age, 43.8 [14.6] years). Median (IQR) duration between primary COVID-19 vaccination and sample collection was 146 (47-189) days. Prevaccination samples had high levels of anti-MERS S1 immunoglobin M (IgM) and IgG (reactivity index ranging from 0.80 to 54.7 for IgM and from 0.85 to 176.3 for IgG). Cross-reactive antibodies with SARS-CoV and SARS-CoV-2 were also detected in these samples. However, cross-reactivity against other coronaviruses was not detected by the microarray assay. Postvaccination samples showed significantly higher levels of total antibodies, IgG, and IgA targeting SARS-CoV-2 S protein compared with prevaccination samples (eg, mean total antibodies: 8955.0 AU/mL; 95% CI, -5025.0 to 22936.0 arbitrary units/mL; P = .002). In addition, significantly higher anti-SARS S1 IgG levels were detected following vaccination (mean reactivity index, 55.4; 95% CI, -9.1 to 120.0; P = .001), suggesting potential cross-reactivity with these coronaviruses. Also, anti-S NAbs were significantly boosted against SARS-CoV-2 (50.5% neutralization; 95% CI, 17.6% to 83.2% neutralization; P < .001) after vaccination. Furthermore, there was no significant increase in antibody-dependent cellular cytotoxicity against SARS-CoV-2 S protein postvaccination.Conclusions and relevanceThis cohort study found a significant boost in cross-reactive NAbs in some patients exposed to MERS-CoV and SARS-CoV-2 antigens. These findings suggest that isolation of broadly reactive antibodies from these patients may help guide the development of a pancoronavirus vaccine by targeting cross-reactive epitopes between distinct strains of human coronaviruses.

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

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Cross-reactive CD4<sup>+</sup> T cells enhance SARS-CoV-2 immune responses upon infection and vaccination.

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

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Cross-reactive CD4<sup>+</sup> T cells enhance SARS-CoV-2 immune responses upon infection and vaccination.

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OmicsDI is part of the ELIXIR infrastructure

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