Hybrid immunity-based induction of durable pan-endemic-coronavirus immunity in the elderly
Repeated vaccinations and infections have led to diverse states of hybrid immunity against SARS-CoV-2 in the global population. However, age and comorbidities can compromise protection against severe disease, and antibody-mediated immunity is undercut by viral immune escape mutations. Whether and to what extent durable T cell responses compensate for reduced humoral immunity, particularly in the elderly, have not been investigated. Here, we utilize SARS-CoV-2-specific and pan-coronavirus-derived peptide pools, including or excluding spike glycoprotein-derived epitopes, to measure vaccination and infection induced pan-human endemic coronavirus (PHEC)-directed T cell immunity. In contrast to vaccinated individuals, hybrid immunity induced by vaccination and SARS-CoV-2 infection comprises high frequencies of PHEC-reactive T cells with comparable frequencies and functional TCR avidities across all age groups. With waning humoral immunity and vulnerability to escape mutations, PHEC-reactive T cells may provide critical protection. Our findings underscore the importance of incorporating pan-coronavirus T cell epitopes in future vaccine strategies.
Authors
- Wibke Johannis (ORCID: https://orcid.org/0000-0002-2886-7306)
- Marica Grossegesse (ORCID: https://orcid.org/0000-0002-9369-8203)
- Karsten Schnatbaum (ORCID: https://orcid.org/0000-0002-2840-6294)
- Andreas Nitsche (ORCID: https://orcid.org/0000-0001-8185-3176)
- Veronica Di Cristanziano (ORCID: https://orcid.org/0000-0003-1604-8386)
- Manuela Dingeldey (ORCID: https://orcid.org/0000-0001-8412-3910)
- Julian Braun (ORCID: https://orcid.org/0000-0002-7788-8154)
- Maike Mangold (ORCID: https://orcid.org/0000-0002-4547-7246)
- Leif Erik Sander (ORCID: https://orcid.org/0000-0002-0476-9947)
- Larissa Henze (ORCID: https://orcid.org/0000-0002-6540-4263)
- Beate Kruse
- Lucie Loyal (ORCID: https://orcid.org/0000-0001-5738-4437)
- Andreas Thiel (ORCID: https://orcid.org/0000-0002-5515-4002)
- Peiley Lau (ORCID: https://orcid.org/0000-0002-9338-2006)
- Janina Behrens (ORCID: https://orcid.org/0000-0002-9723-8087)
- Lil Meyer‐Arndt (ORCID: https://orcid.org/0000-0002-7909-020X)
- Janine Michel (ORCID: https://orcid.org/0000-0001-6227-3125)
- Holger Wenschuh
- Ulf Reimer (ORCID: https://orcid.org/0000-0002-3375-6889)
- Florian Klein (ORCID: https://orcid.org/0000-0003-1376-1792)
Institutions
- University of Cologne (DE)
- Robert Koch Institute (DE)
- Humboldt-Universität zu Berlin (DE)
- JPT Peptide Technologies (Germany) (DE)
- Berlin Institute of Health at Charité - Universitätsmedizin Berlin (DE)
- University Hospital Cologne (DE)
Publication Details
- Journal
- Cell Reports
- Published
- 2025-02-01
- DOI
- https://doi.org/10.1016/j.celrep.2025.115314
- Citations
- 4
- Primary Topic
- SARS-CoV-2 and COVID-19 Research
- Type
- article
- Field-Weighted Citation Impact
- 5.58