T-cell recognition of SARS-CoV-2 antigen peptides following booster vaccination with mRNA and viral-vectored COVID-19 vaccines
- 1Department of Immunology, Noguchi Memorial Institute for Medical Research, College of Health Sciences, University of Ghana , ,
- 2West African Centre for Cell Biology of Infectious Pathogens, College of Basic and Applied Sciences, University of Ghana , ,
- 3Department of Microbiology and Immunology, School of Medical Sciences, University of Cape Coast , ,
Abstract
Background: Durability and breadth of SARS-CoV-2-specific T-cell responses following booster vaccination remain key to guiding next-generation vaccine design, especially in the context of waning antibodies, emerging variants, and diverse immunological backgrounds. This longitudinal study assessed IFN-γ-producing T-cell responses in 46 fully vaccinated adults who received a booster dose of either the BNT162b2 (mRNA) or Ad26.COV2.S (adenoviral vector) vaccine. All participants were nucleocapsid-seropositive at baseline, with antibody levels stable throughout follow-up, indicating prior natural infection and no incident infection during the study period.
Methods: Using an ex vivo IFN-γ ELISpot assay, responses were measured at four timepoints (baseline, Months 3, 6 and 9) against spike (S; n = 46) and nucleocapsid (N; n = 16) peptides selected by NetMHCpan-4.1 prediction from overlapping 15-mer libraries spanning both proteins. Each peptide was tested individually, allowing every response to be assigned to a defined sequence. Longitudinal change was modelled using linear mixed-effects models, comparing total with median per-peptide responses to distinguish loss of specificities from loss of per-epitope strength. Analyses were stratified by booster type and vaccination strategy (homologous vs. heterologous).
Results: Time strongly affected total S-specific IFN-γ responses (F(3, 96.6) = 33.16, p = 8 × 10−15) but not median per-peptide responses (F(3, 95.8) = 0.62, p = 0.606), indicating that the decline reflected contraction in the number of epitopes recognized rather than weakening of individual responses; the same dissociation held within both booster groups. Ad26.COV2.S boosting was associated with broader S-specific epitope recognition and greater durability, with a subset of responses persisting through Month 9, whereas BNT162b2 recipients showed higher cumulative IFN-γ magnitude through Month 6 — a difference already present before boosting (p = 0.012). N-specific responses declined despite stable anti-nucleocapsid antibody, although two N-derived regions (YGANKDGIIW, VTPSGTWLTY) were recognized at every timepoint.
Discussion/conclusions: Booster platform and vaccination strategy shaped the magnitude, breadth and durability of SARS-CoV-2-specific T-cell responses, with the longitudinal decline appearing to be driven predominantly by narrowing of epitope breadth among Month 3-reactive peptides rather than reduced per-epitope function. The persistently immunogenic S and N epitopes identified here warrant further evaluation as candidates for multi-epitope T-cell vaccine design.
Related
- Mutations that positively affect Bandavirus glycoprotein function in VSV-vectored vaccines
- Safety and immunogenicity of a first-generation modified vaccinia virus Ankara-vectored SARS-CoV-2 vaccine candidate with mRNA-based booster vaccination: A phase 1 trial.
- Cost-effectiveness of 20-valent versus 15-valent pneumococcal conjugate vaccines for infants in the Netherlands, taking into account indirect effects and adult vaccination
- Immunogenicity and safety of an interchangeable vaccination schedule of two inactivated Japanese encephalitis vaccines: a multicentric, phase IV, open-label, randomized controlled trial
- Combined Vaccination with Recombinant HVT-ND and Live Newcastle Disease Vaccines Accelerates Early Immunity, Limits Virus Shedding and Reduces Transmission.
BibTeX
@article{maru2026tcell,
title = {{T-cell recognition of SARS-CoV-2 antigen peptides following booster vaccination with mRNA and viral-vectored COVID-19 vaccines}},
author = {Adams Kiplimo Maru and Precious Kwesi Kumi and Abigail Naa Adjorkor Pobee and Nana Yaa Asiedua Appiah and Nana Akua Obiribea Koranteng and Theophilus Brenko and Frank Osei and Doreen Teye-Adjei and Georgina Agyekum and Linda Akuffo and Francis Dzabeng and Eric Kyei-Baafour and Dorcas Obiri-Yeboah and Yaw Aniweh and Michael Fokuo Ofori and Kwadwo Asamoah Kusi and Frederica Dedo Partey},
journal = {Frontiers in cellular and infection microbiology},
year = {2026},
month = oct,
doi = {10.3389/fcimb.2026.1947651},
url = {https://europepmc.org/article/PMC/PMC13724500},
note = {CC BY},
}
RIS
TY - JOUR
TI - T-cell recognition of SARS-CoV-2 antigen peptides following booster vaccination with mRNA and viral-vectored COVID-19 vaccines
AU - Adams Kiplimo Maru
AU - Precious Kwesi Kumi
AU - Abigail Naa Adjorkor Pobee
AU - Nana Yaa Asiedua Appiah
AU - Nana Akua Obiribea Koranteng
AU - Theophilus Brenko
AU - Frank Osei
AU - Doreen Teye-Adjei
AU - Georgina Agyekum
AU - Linda Akuffo
AU - Francis Dzabeng
AU - Eric Kyei-Baafour
AU - Dorcas Obiri-Yeboah
AU - Yaw Aniweh
AU - Michael Fokuo Ofori
AU - Kwadwo Asamoah Kusi
AU - Frederica Dedo Partey
PY - 2026
DA - 2026/10/19
JO - Frontiers in cellular and infection microbiology
DO - 10.3389/fcimb.2026.1947651
UR - https://europepmc.org/article/PMC/PMC13724500
AB - Background: Durability and breadth of SARS-CoV-2-specific T-cell responses following booster vaccination remain key to guiding next-generation vaccine design, especially in the context of waning antibodies, emerging variants, and diverse immunological backgrounds. This longitudinal study assessed IFN-γ-producing T-cell responses in 46 fully vaccinated adults who received a booster dose of either the BNT162b2 (mRNA) or Ad26.COV2.S (adenoviral vector) vaccine. All participants were nucleocapsid-seropositive at baseline, with antibody levels stable throughout follow-up, indicating prior natural infection and no incident infection during the study period. Methods: Using an ex vivo IFN-γ ELISpot assay, responses were measured at four timepoints (baseline, Months 3, 6 and 9) against spike (S; n = 46) and nucleocapsid (N; n = 16) peptides selected by NetMHCpan-4.1 prediction from overlapping 15-mer libraries spanning both proteins. Each peptide was tested individually, allowing every response to be assigned to a defined sequence. Longitudinal change was modelled using linear mixed-effects models, comparing total with median per-peptide responses to distinguish loss of specificities from loss of per-epitope strength. Analyses were stratified by booster type and vaccination strategy (homologous vs. heterologous). Results: Time strongly affected total S-specific IFN-γ responses (F(3, 96.6) = 33.16, p = 8 × 10−15) but not median per-peptide responses (F(3, 95.8) = 0.62, p = 0.606), indicating that the decline reflected contraction in the number of epitopes recognized rather than weakening of individual responses; the same dissociation held within both booster groups. Ad26.COV2.S boosting was associated with broader S-specific epitope recognition and greater durability, with a subset of responses persisting through Month 9, whereas BNT162b2 recipients showed higher cumulative IFN-γ magnitude through Month 6 — a difference already present before boosting (p = 0.012). N-specific responses declined despite stable anti-nucleocapsid antibody, although two N-derived regions (YGANKDGIIW, VTPSGTWLTY) were recognized at every timepoint. Discussion/conclusions: Booster platform and vaccination strategy shaped the magnitude, breadth and durability of SARS-CoV-2-specific T-cell responses, with the longitudinal decline appearing to be driven predominantly by narrowing of epitope breadth among Month 3-reactive peptides rather than reduced per-epitope function. The persistently immunogenic S and N epitopes identified here warrant further evaluation as candidates for multi-epitope T-cell vaccine design.
SN - 2235-2988
ER -