{ "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.\n\nMethods: 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).\n\nResults: 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.\n\nDiscussion/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.", "abstract_shown": true, "affiliations": [ "Department of Immunology, Noguchi Memorial Institute for Medical Research, College of Health Sciences, University of Ghana , ,", "West African Centre for Cell Biology of Infectious Pathogens, College of Basic and Applied Sciences, University of Ghana , ,", "Department of Microbiology and Immunology, School of Medical Sciences, University of Cape Coast , ," ], "article_type": "research article", "arxiv": null, "author_total": 17, "authors": [ { "affs": [ 0 ], "name": "Adams Kiplimo Maru" }, { "affs": [ 0 ], "name": "Precious Kwesi Kumi" }, { "affs": [ 0 ], "name": "Abigail Naa Adjorkor Pobee" }, { "affs": [ 0 ], "name": "Nana Yaa Asiedua Appiah" }, { "affs": [ 0 ], "name": "Nana Akua Obiribea Koranteng" }, { "affs": [ 0 ], "name": "Theophilus Brenko" }, { "affs": [ 0 ], "name": "Frank Osei" }, { "affs": [ 0 ], "name": "Doreen Teye-Adjei" }, { "affs": [ 0 ], "name": "Georgina Agyekum" }, { "affs": [ 0 ], "name": "Linda Akuffo" }, { "affs": [ 1 ], "name": "Francis Dzabeng" }, { "affs": [ 0 ], "name": "Eric Kyei-Baafour" }, { "affs": [ 2 ], "name": "Dorcas Obiri-Yeboah" }, { "affs": [ 1 ], "name": "Yaw Aniweh" }, { "affs": [ 0 ], "name": "Michael Fokuo Ofori" }, { "affs": [ 0 ], "name": "Kwadwo Asamoah Kusi" }, { "affs": [ 0 ], "name": "Frederica Dedo Partey" } ], "bibtex": "https://research.draconitic.com/paper/3pajetk5rj6th.bib", "cited_by": 0, "doi": "10.3389/fcimb.2026.1947651", "fulltext_url": "https://www.ncbi.nlm.nih.gov/pmc/articles/PMC13724500/?tool=EBI", "id": "3pajetk5rj6th", "issns": [ "2235-2988" ], "landing_url": "https://europepmc.org/article/PMC/PMC13724500", "language": "eng", "licence": "CC-BY", "licence_label": "CC BY", "licence_source": "article", "licence_url": "https://creativecommons.org/licenses/by/4.0/", "metadata_licence": null, "native_subjects": [ [ "heading", "Original Research" ], [ "openalex", "2725|SARS-CoV-2 and COVID-19 Research" ] ], "openalex": "W7222926305", "pdf_url": "https://www.ncbi.nlm.nih.gov/pmc/articles/PMC13724500/pdf/?tool=EBI", "pmcid": "PMC13724500", "pmid": "42973757", "published": "2026-10-19", "publisher": "Frontiers Media SA", "ris": "https://research.draconitic.com/paper/3pajetk5rj6th.ris", "sources": [ { "first_seen": "2026-11-03T15:20:51Z", "native_id": "PMC:PMC13724500", "source": "europepmc", "url": "https://europepmc.org/article/PMC/PMC13724500" }, { "first_seen": "2026-11-04T12:23:03Z", "native_id": "PMC13724500", "source": "pmc", "url": "https://doi.org/10.3389/fcimb.2026.1947651" }, { "first_seen": "2026-11-04T15:20:48Z", "native_id": "MED:42973757", "source": "europepmc", "url": "https://europepmc.org/article/MED/42973757" } ], "subjects": [ { "field": "medicine", "origin": "openalex:2725|SARS-CoV-2 and COVID-19 Research", "subfield": "infectious-disease" } ], "title": "T-cell recognition of SARS-CoV-2 antigen peptides following booster vaccination with mRNA and viral-vectored COVID-19 vaccines", "title_text": "T-cell recognition of SARS-CoV-2 antigen peptides following booster vaccination with mRNA and viral-vectored COVID-19 vaccines", "type": "peer-reviewed", "updated_at": "2026-11-06T12:20:57Z", "url": "https://research.draconitic.com/paper/3pajetk5rj6th", "venue": "Frontiers in cellular and infection microbiology", "versions": [] }