Cutting Edge: Serum but Not Mucosal Antibody Responses Are Associated with Pre-Existing SARS-CoV-2 Spike Cross-Reactive CD4+ T Cells following BNT162b2 Vaccination in the Elderly

Author:

Meyer-Arndt Lil12345,Schwarz Tatjana6ORCID,Loyal Lucie12ORCID,Henze Larissa12ORCID,Kruse Beate12,Dingeldey Manuela12,Gürcan Kübrah7ORCID,Uyar-Aydin Zehra7ORCID,Müller Marcel A.6,Drosten Christian6,Paul Friedemann25,Sander Leif E.8,Demuth Ilja910,Lauster Roland7,Giesecke-Thiel Claudia11ORCID,Braun Julian12ORCID,Corman Victor M.6ORCID,Thiel Andreas12ORCID

Affiliation:

1. *Si–M/‘Der Simulierte Mensch’, Technische Universität Berlin and Charité – Universitätsmedizin Berlin, Berlin, Germany;

2. †Charité – Universitätsmedizin Berlin, Berliner Institut für Gesundheitsforschung, Immunomics, Regenerative Immunologie und Altern, Berlin, Germany;

3. ‡Charité – Universitätsmedizin Berlin, NeuroCure Clinical Research Center, Berlin, Germany;

4. §Charité – Universitätsmedizin Berlin, Klinik für Neurologie mit Experimenteller Neurologie, Berlin, Germany;

5. ¶Charité – Universitätsmedizin Berlin and Max-Delbrück-Centrum für Molekulare Medizin, Experimental and Clinical Research Center, Berlin, Germany;

6. ‖Charité – Universitätsmedizin Berlin, Institut für Virologie, Berlin, Germany;

7. #Medizinische Biotechnologie, Institut für Biotechnologie, Technische Universität Berlin, Berlin, Germany;

8. **Charité – Universitätsmedizin Berlin, Klinik für Infektiologie und Pneumologie, Berlin, Germany;

9. ††Charité – Universitätsmedizin Berlin, Klinik für Endokrinologie und Stoffwechselmedizin, Biologie des Alterns, Berlin, Germany;

10. ‡‡Berliner Institut für Gesundheitsforschung der Charité – Universitätsmedizin Berlin, Centrum für Regenerative Therapien, Berlin, Germany; and

11. §§Max Planck Institute for Molecular Genetics, Berlin, Germany

Abstract

Abstract Advanced age is a main risk factor for severe COVID-19. However, low vaccination efficacy and accelerated waning immunity have been reported in this age group. To elucidate age-related differences in immunogenicity, we analyzed human cellular, serological, and salivary SARS-CoV-2 spike glycoprotein-specific immune responses to the BNT162b2 COVID-19 vaccine in old (69–92 y) and middle-aged (24–57 y) vaccinees compared with natural infection (COVID-19 convalescents, 21–55 y of age). Serological humoral responses to vaccination excee-ded those of convalescents, but salivary anti-spike subunit 1 (S1) IgA and neutralizing capacity were less durable in vaccinees. In old vaccinees, we observed that pre-existing spike-specific CD4+ T cells are associated with efficient induction of anti-S1 IgG and neutralizing capacity in serum but not saliva. Our results suggest pre-existing SARS-CoV-2 cross-reactive CD4+ T cells as a predictor of an efficient COVID-19 vaccine-induced humoral immune response in old individuals.

Funder

German Federal Ministry of Education and Research

German Federal Ministry of Health

Deutsche Forschungsgemeinschaft

Publisher

The American Association of Immunologists

Subject

Immunology,Immunology and Allergy

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