{"doi":"10.1101/2023.10.28.23297714","title":"Post-pandemic memory T-cell response to SARS-CoV-2 is durable, broadly targeted and cross-reactive to hypermutated BA.2.86","abstract":"SUMMARY The COVID-19 post-pandemic period is characterised by infection waves of uncertain size (due to low rates of SARS-CoV-2 testing and notification), as well as limited uptake or global access to updated variant vaccines. Ongoing SARS-CoV-2 evolution has given rise to recombinant Omicron lineages that dominate globally (XBB.1), as well as the emergence of hypermutated variants (BA.2.86). In this context, durable and cross-reactive T-cell immune memory is critical for continued protection against severe COVID-19. We examined T-cell responses to SARS-CoV-2 approximately 1.5 years since Omicron first emerged. We describe sustained CD4+ and CD8+ spike-specific T-cell memory responses in healthcare workers in South Africa (n=39), most of whom had received 2 doses of Ad26.CoV2.S (Johnson & Johnson/Janssen) vaccine and experienced at least one SARS-CoV-2 infection. Spike-specific T cells were highly cross-reactive with all Omicron variants tested, including BA.2.86. Abundant non-spike (nucleocapsid and membrane)-specific T cells were detectable in most participants, augmenting the total T-cell resources available for protection. The bulk of SARS-CoV-2-specific T-cell responses had an early-differentiated phenotype, explaining their persistent nature. Thus, hybrid immunity leads to the accumulation of spike and non-spike T cells evident 3.5 years after the start of the pandemic, with preserved recognition of highly mutated SARS-CoV-2 variants. Long-term T-cell immune memory is likely to provide continued protection against severe outcomes of COVID-19. In Brief Nesamari et al. investigate T-cell responses in the context of hybrid immunity 3.5 years after the start of the COVID-19 pandemic. They show that T-cell memory is highly durable and cross-reactive with recombinant variants XBB.1 and hypermutated BA.2.86. Abundant non-spike responses augment the overall T-cell response.","journal":"medRxiv","year":2023,"id":393778,"datarank":0.0,"base_score":0.0,"endowment":0.0,"self_citation_contribution":0.0,"citation_network_contribution":0.0,"self_endowment_contribution":0.0,"citer_contribution":0.0,"corpus_percentile":null,"corpus_rank":null,"citation_count":4,"citer_count":0,"citers_with_citation_signal":0,"citers_with_endowment":0,"datacite_reuse_total":0,"is_dataset":false,"is_dataset_confidence":0.9484,"is_data_producer":false,"deposit_databanks":null,"is_oa":true,"file_count":0,"downloads":0,"has_version_chain":false,"published_date":"2023-01-01","fair_score":null,"fair_percentile":null,"algorithm_id":"datarank_citation_only_1hop_v6","ranking_scope":"data_only","authors":[{"id":958409,"name":"Millicent A. Omondi","orcid":"0000-0003-1332-2167","position":1,"is_corresponding":false},{"id":1024216,"name":"Maxine A. 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Magugu","orcid":null,"position":7,"is_corresponding":false},{"id":1166739,"name":"Paballo Mosala","orcid":null,"position":8,"is_corresponding":false},{"id":1098097,"name":"Avril Walters","orcid":null,"position":9,"is_corresponding":false},{"id":1167880,"name":"G Clark","orcid":"0000-0002-1717-5718","position":10,"is_corresponding":false},{"id":633150,"name":"Mathilda Mennen","orcid":"0009-0006-1169-4812","position":11,"is_corresponding":false},{"id":633865,"name":"Sango Skelem","orcid":null,"position":12,"is_corresponding":false},{"id":804016,"name":"Marguerite Adriaanse","orcid":"0009-0001-2895-8160","position":13,"is_corresponding":false},{"id":292649,"name":"Alba Grifoni","orcid":"0000-0002-2209-5966","position":14,"is_corresponding":false},{"id":55670,"name":"Alessandro Sette","orcid":"0000-0001-7013-2250","position":15,"is_corresponding":false},{"id":633143,"name":"Roanne Keeton","orcid":"0000-0003-4808-9756","position":16,"is_corresponding":false},{"id":91456,"name":"Ntobeko A. B. Ntusi","orcid":"0000-0003-2347-7883","position":17,"is_corresponding":false},{"id":330707,"name":"Catherine Riou","orcid":"0000-0001-9679-0745","position":18,"is_corresponding":false},{"id":584841,"name":"Wendy A. Burgers","orcid":"0000-0003-3396-9398","position":19,"is_corresponding":false},{"id":1166740,"name":"Rofhiwa Nesamari","orcid":null,"position":0,"is_corresponding":true}],"reference_count":41,"raw_metadata":null,"created_at":"2026-07-19T01:19:05.913428Z","pmid":null,"pmcid":null,"fwci":null,"citation_percentile":null,"influential_citations":0,"oa_status":null,"license":null,"views":0,"total_file_size_bytes":0,"version_count":0,"fair_f":null,"fair_a":null,"fair_i":null,"fair_r":null,"fair_zscore":null,"fair_rationale":null,"fair_model":null,"fair_agent_version":null,"fair_fulltext_source":null,"fair_has_llm":null,"fair_computed_at":null,"clinical_trials":[],"software_tools":[],"db_accessions":[],"linked_datasets":[],"topics":[]}