Initial antigen encounter determines robust T-cell immunity against SARS-CoV-2 BA.2.86 variant three years later
Year: 2024
Type: article
Study design: Observational Study
Abstract: OBJECTIVES: We aimed to evaluate the adaptive immune responses cross-recognition of the hypermutated SARS-CoV-2 BA.2.86 variant and identify the determinants influencing this recognition. METHODS: We measured BA.2.86 neutralizing antibodies and T-cell responses cross-reactivity in previously exposed participants. We investigated clinical-demographic factors and used a novel in silico analysis to assess viral genetic determinants affecting T-cell responses. RESULTS: Despite notable escape from neutralizing antibodies, T-cell responses remained generally preserved, albeit with a significant but small loss in T-cell cross-recognition (7.5%, 14.2%, and 10.8% average loss for IFN-γ, IL-2, and IFN-γ + IL-2, respectively, p<0.05). This is consistent with the prediction of 6 out of 10 immunodominant T-cell epitopes (TCEs) altered by BA.2.86 mutations to have reduced peptide presentation. This effect is expected to be mitigated by total TCEs across the genome. Remarkably, T-cell responses and cross-recognition were 3.5 (IFN-γ), 2 (IL-2) and 2.4 (IFN-γ + IL-2) times higher when first induced by infection rather than by vaccination three years earlier, by increasing number of infections, and by ancestral/Delta than Omicron infections. CONCLUSIONS: Our findings underscore the critical role and factors influencing T-cell immunity against evolving SARS-CoV-2 variants, such as first antigen encounter (vaccination or infection), as it is essential for developing effective control strategies.
Source: Journal of Infection
Authors: Rocío Rubio, Alexei Yavlinsky, Marina Escalera Zamudio, Luis M. Molinos-Albert, Carla Martín Pérez, Edwards Pradenas, Mar Canyelles, Cèlia Torres, Cedric Tan, Leo Swadling, Anna Ramírez-Morros, Benjamin Trinité, Josep Vidal-Alaball, Ruth Aguilar, Anna Ruiz-Comellas, Julià Blanco, Lucy van Dorp, François Balloux, Carlota Dobaño, Gemma Moncunill
Institutions: Barcelona Institute for Global Health, Universitat de Barcelona, University College London, IrsiCaixa, Institut Universitari d'Investigació en Atenció Primària Jordi Gol, Institut Català de la Salut, Universitat de Vic - Universitat Central de Catalunya, Instituto de Salud Carlos III, Centro de Investigación Biomédica en Red Enfermedades Infecciosas
Language: English
Subfield: Infectious Diseases
Field: Medicine
Domain: Health Sciences
Open Access status: gold
Estimated APC paid: $4,030
Funders: Arkansas Department of Health, Centres de Recerca de Catalunya, National Institute for Health and Care Research, European Commission, Rosetrees Trust, Generalitat de Catalunya, Ministerio de Ciencia e Innovación, Fundació Privada Daniel Bravo Andreu, Departament de Salut, Generalitat de Catalunya, Agencia Estatal de Investigación, European Social Fund, Pears Foundation
Awards: G1175115578, G1320557761, G2064873908, G210041235, G2114305129, G2262748287, G2601397997, G2792670919, G2819494518, G290270322, G2912995829, G3005324705, G300979063, G3288897321, G34346518, G3480869486, G3681454997, G4016763146, G4042783231, G425668148, G5080475149, G6054710752, G6218905885, G630635040, G6656126374, G6857728958, G69051668, G6933787748, G7084143925, ENDING COVID 19 VARIANTS OF CONCERN THROUGH COHORT STUDIES: END-VOC
OpenAlex ID: W4405931504