Multi-antigen coronavirus vaccine induces potent and durable cross-protection against multiple SARS-CoV-2 variants.
8 affiliations
- 1Laboratory of Cellular and Molecular Immunology, Gavin Herbert Eye Institute, School of Medicine, University of California, Irvine, Irvine, CA, USA.
- 2Department of Vaccines and Immunotherapies, TechImmune, LLC, University Lab Partners, Irvine, CA, USA.
- 3BSL-3 Laboratories, High Containment Core Facility, School of Medicine, University of California, Irvine, Irvine, USA.
- 4Department of Pathology and Laboratory Medicine, School of Medicine, Irvine, CA, USA.
- 5Department of Surgery, Divisions of Trauma, Burns & Critical Care, School of Medicine, Irvine, CA, USA.
- 6Laboratory of Cellular and Molecular Immunology, Gavin Herbert Eye Institute, School of Medicine, University of California, Irvine, Irvine, CA, USA. [email protected].
- 7Department of Vaccines and Immunotherapies, TechImmune, LLC, University Lab Partners, Irvine, CA, USA. [email protected].
- 8Institute for Immunology, School of Medicine, University of California, Irvine, Irvine, CA, USA. [email protected].
Abstract
The first-generation Spike-based COVID-19 vaccines reduced the risk of hospitalization, serious illness, and death from SARS-CoV-2 infections. However, waning immunity failed to prevent immune escape, resulting in multiple variants of concern (VOCs) and prolonging the pandemic. We hypothesize that next-generation CoV vaccines incorporating highly conserved SARS-CoV-2 T cell antigens would confer potent, broad, long-lasting cross-protective immunity against multiple VOCs. In this study, we identified 10 non-Spike antigens common and highly conserved across 8.7 million SARS-CoV-2 strains, prior VOCs, SARS-CoV-1, MERS-CoV, seasonal human cold CoVs, and animal CoVs. Seven antigens were preferentially recognized by CD8⁺ and CD4⁺ T cells from unvaccinated asymptomatic COVID-19 patients, irrespective of VOC. Three conserved antigens (NSP2, NSP14, Nucleoprotein) administered to golden Syrian hamsters: (i) induced high frequencies of lung-resident polyfunctional CXCR5⁺CD4⁺ TFH cells, GzmB⁺CD4⁺/CD8⁺ cytotoxic T cells, and CD69⁺IFN-γ⁺TNFα⁺CD4⁺/CD8⁺ effector T cells; (ii) reduced morbidity, viral load, lung pathology, and COVID-19-like symptoms from various VOCs, including the pathogenic B.1.617.2 Delta and the recent KP.3 Omicron variants; (iii) improved protection conferred by spike-alone mRNA; and (iv) conferred protection that lasted for more than 1 year. This multi-antigen CoV vaccine could provide potent, broad-spectrum, and durable cross-protective immunity against current and future variants of concern in the clinic.
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BibTeX
@article{prakash2026multiantigen,
title = {{Multi-antigen coronavirus vaccine induces potent and durable cross-protection against multiple SARS-CoV-2 variants.}},
author = {Swayam Prakash and Nisha R Dhanushkodi and Afshana Quadiri and Hawa Vahed and Aziz A Chentoufi and Pierre-Gregoire Coulon and Izabela Coimbra Ibraim and Assia El Babsiri and Delia F Tifrea and Cesar J Figueroa and Daniel Gil and Jeffrey B Ulmer and Lbachir BenMohamed},
journal = {NPJ vaccines},
year = {2026},
month = aug,
doi = {10.1038/s41541-026-01549-y},
url = {https://europepmc.org/article/MED/42834091},
note = {CC BY},
}
RIS
TY - JOUR
TI - Multi-antigen coronavirus vaccine induces potent and durable cross-protection against multiple SARS-CoV-2 variants.
AU - Swayam Prakash
AU - Nisha R Dhanushkodi
AU - Afshana Quadiri
AU - Hawa Vahed
AU - Aziz A Chentoufi
AU - Pierre-Gregoire Coulon
AU - Izabela Coimbra Ibraim
AU - Assia El Babsiri
AU - Delia F Tifrea
AU - Cesar J Figueroa
AU - Daniel Gil
AU - Jeffrey B Ulmer
AU - Lbachir BenMohamed
PY - 2026
DA - 2026/08/18
JO - NPJ vaccines
DO - 10.1038/s41541-026-01549-y
UR - https://europepmc.org/article/MED/42834091
AB - The first-generation Spike-based COVID-19 vaccines reduced the risk of hospitalization, serious illness, and death from SARS-CoV-2 infections. However, waning immunity failed to prevent immune escape, resulting in multiple variants of concern (VOCs) and prolonging the pandemic. We hypothesize that next-generation CoV vaccines incorporating highly conserved SARS-CoV-2 T cell antigens would confer potent, broad, long-lasting cross-protective immunity against multiple VOCs. In this study, we identified 10 non-Spike antigens common and highly conserved across 8.7 million SARS-CoV-2 strains, prior VOCs, SARS-CoV-1, MERS-CoV, seasonal human cold CoVs, and animal CoVs. Seven antigens were preferentially recognized by CD8⁺ and CD4⁺ T cells from unvaccinated asymptomatic COVID-19 patients, irrespective of VOC. Three conserved antigens (NSP2, NSP14, Nucleoprotein) administered to golden Syrian hamsters: (i) induced high frequencies of lung-resident polyfunctional CXCR5⁺CD4⁺ TFH cells, GzmB⁺CD4⁺/CD8⁺ cytotoxic T cells, and CD69⁺IFN-γ⁺TNFα⁺CD4⁺/CD8⁺ effector T cells; (ii) reduced morbidity, viral load, lung pathology, and COVID-19-like symptoms from various VOCs, including the pathogenic B.1.617.2 Delta and the recent KP.3 Omicron variants; (iii) improved protection conferred by spike-alone mRNA; and (iv) conferred protection that lasted for more than 1 year. This multi-antigen CoV vaccine could provide potent, broad-spectrum, and durable cross-protective immunity against current and future variants of concern in the clinic.
SN - 2059-0105
ER -