tetano
Editor, Senior Moderator
Cell Rep
. 2025 Feb 16;44(2):115314.
doi: 10.1016/j.celrep.2025.115314. Online ahead of print. Hybrid immunity-based induction of durable pan-endemic-coronavirus immunity in the elderly
Lucie Loyal[SUP] 1 [/SUP], Julian Braun[SUP] 1 [/SUP], Ulf Reimer[SUP] 2 [/SUP], Lil Meyer-Arndt[SUP] 3 [/SUP], Larissa Henze[SUP] 1 [/SUP], Beate Kruse[SUP] 1 [/SUP], Manuela Dingeldey[SUP] 1 [/SUP], Maike Mangold[SUP] 1 [/SUP], Janina Behrens[SUP] 1 [/SUP], Pinkus Tober Lau[SUP] 4 [/SUP], Janine Michel[SUP] 5 [/SUP], Marica Grossegesse[SUP] 5 [/SUP], Karsten Schnatbaum[SUP] 2 [/SUP], Holger Wenschuh[SUP] 2 [/SUP], Wibke Johannis[SUP] 6 [/SUP], Veronica Di Cristanziano[SUP] 7 [/SUP], Andreas Nitsche[SUP] 5 [/SUP], Florian Klein[SUP] 7 [/SUP], Leif-Erik Sander[SUP] 8 [/SUP], Andreas Thiel[SUP] 9 [/SUP]
Affiliations
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.
Keywords: CP: Immunology; SARS-CoV-2; T cell responses; aging; antibody titers; avidity; cross-reactivity; endemic coronaviruses; epitopes; hybrid immunity; polyfunctionality.
. 2025 Feb 16;44(2):115314.
doi: 10.1016/j.celrep.2025.115314. Online ahead of print. Hybrid immunity-based induction of durable pan-endemic-coronavirus immunity in the elderly
Lucie Loyal[SUP] 1 [/SUP], Julian Braun[SUP] 1 [/SUP], Ulf Reimer[SUP] 2 [/SUP], Lil Meyer-Arndt[SUP] 3 [/SUP], Larissa Henze[SUP] 1 [/SUP], Beate Kruse[SUP] 1 [/SUP], Manuela Dingeldey[SUP] 1 [/SUP], Maike Mangold[SUP] 1 [/SUP], Janina Behrens[SUP] 1 [/SUP], Pinkus Tober Lau[SUP] 4 [/SUP], Janine Michel[SUP] 5 [/SUP], Marica Grossegesse[SUP] 5 [/SUP], Karsten Schnatbaum[SUP] 2 [/SUP], Holger Wenschuh[SUP] 2 [/SUP], Wibke Johannis[SUP] 6 [/SUP], Veronica Di Cristanziano[SUP] 7 [/SUP], Andreas Nitsche[SUP] 5 [/SUP], Florian Klein[SUP] 7 [/SUP], Leif-Erik Sander[SUP] 8 [/SUP], Andreas Thiel[SUP] 9 [/SUP]
Affiliations
- PMID: 39960834
- DOI: 10.1016/j.celrep.2025.115314
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.
Keywords: CP: Immunology; SARS-CoV-2; T cell responses; aging; antibody titers; avidity; cross-reactivity; endemic coronaviruses; epitopes; hybrid immunity; polyfunctionality.