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CC BY-NC-ND V4.0, Open Access
Journal article
Highly conserved Betacoronavirus sequences are broadly recognized by human T cells
Cell, Vol.188(20), pp.5653-5665.E12
2025
PMID: 40774254
Abstract
The COVID-19 pandemic highlighted the critical need for vaccine strategies capable of addressing emerging viral threats. Betacoronaviruses, including severe acute respiratory syndrome coronavirus (SARS-CoV), Middle East respiratory syndrome (MERS), and SARS-CoV-2, present significant pandemic risks due to their zoonotic potential and genetic diversity. T cell-mediated immunity has demonstrated durable responses and strong cross-reactivity, offering a promising avenue for achieving broad immunity within a viral family. In this study, we combined comprehensive epitope mapping with sequence conservation analyses to identify conserved T cell epitope regions (CTERs), which constitute 12% of the complete SARS-CoV-2 proteome. We showed that SARS-CoV-2 CTER-specific T cells cross-reactively recognize sequences from multiple Betacoronavirus subgenera. Importantly, incorporating CTERs from non-spike proteins significantly enhanced T cell cross-reactivity potential and human leukocyte antigen (HLA) coverage compared with T cells targeting only spike proteins. Our findings lay the groundwork for a multi-antigen vaccine strategy that includes non-spike proteins to expand cross-reactive immunity across a broader spectrum of Betacoronaviruses.
Details
- Title
- Highly conserved Betacoronavirus sequences are broadly recognized by human T cells
- Authors/Creators
- Tertuliano Alves Pereira Neto - La Jolla Institute for ImmunologyChristian Zmasek - J. Craig Venter InstituteLiliana Avalos - La Jolla Institute for ImmunologyJohn Sidney - La Jolla Institute for ImmunologyRaphael Trevizani - La Jolla Institute for ImmunologyElizabeth Phillips - Institute for Immunology and Infectious Diseases, Murdoch University, Perth, WA, AustraliaSimon Mallal - Institute for Immunology and Infectious Diseases, Murdoch University, Perth, WA, AustraliaApril Frazier - La Jolla Institute for ImmunologyGene S Tan - J. Craig Venter InstituteRichard H Scheuermann - J. Craig Venter InstituteAlessandro Sette - La Jolla Institute for ImmunologyAlba Grifoni - La Jolla Institute for Immunology
- Publication Details
- Cell, Vol.188(20), pp.5653-5665.E12
- Publisher
- Cell Press
- Identifiers
- 991005806848607891
- Copyright
- © 2025 The Author(s).
- Murdoch Affiliation
- Institute for Immunology and Infectious Diseases
- Language
- English
- Resource Type
- Journal article
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