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A Broad-Spectrum Multi-Antigen mRNA/LNP-Based Pan-Coronavirus Vaccine Induced Potent Cross-Protective Immunity Against Infection and Disease Caused by Highly Pathogenic and Heavily Spike-Mutated SARS-CoV-2 Variants of Concern in the Syrian Hamster Model.
Prakash, Swayam; Dhanushkodi, Nisha R; Singer, Mahmoud; Quadiri, Afshana; Zayou, Latifa; Vahed, Hawa; Coulon, Pierre-Gregoire; Ibraim, Izabela Coimbra; Tafoya, Christine; Hitchcock, Lauren; Landucci, Gary; Forthal, Donald N; El Babsiri, Assia; Tifrea, Delia F; Figueroa, Cesar J; Nesburn, Anthony B; Kuppermann, Baruch D; Gil, Daniel; Jones, Trevor M; Ulmer, Jeffrey B; BenMohamed, Lbachir.
Affiliation
  • Prakash S; Laboratory of Cellular and Molecular Immunology, Gavin Herbert Eye Institute, University of California Irvine, School of Medicine, Irvine, CA 92697.
  • Dhanushkodi NR; Laboratory of Cellular and Molecular Immunology, Gavin Herbert Eye Institute, University of California Irvine, School of Medicine, Irvine, CA 92697.
  • Singer M; Laboratory of Cellular and Molecular Immunology, Gavin Herbert Eye Institute, University of California Irvine, School of Medicine, Irvine, CA 92697.
  • Quadiri A; Laboratory of Cellular and Molecular Immunology, Gavin Herbert Eye Institute, University of California Irvine, School of Medicine, Irvine, CA 92697.
  • Zayou L; Laboratory of Cellular and Molecular Immunology, Gavin Herbert Eye Institute, University of California Irvine, School of Medicine, Irvine, CA 92697.
  • Vahed H; Laboratory of Cellular and Molecular Immunology, Gavin Herbert Eye Institute, University of California Irvine, School of Medicine, Irvine, CA 92697.
  • Coulon PG; Department of Vaccines and Immunotherapies, TechImmune, LLC, University Lab Partners, Irvine, CA 92660, USA.
  • Ibraim IC; Laboratory of Cellular and Molecular Immunology, Gavin Herbert Eye Institute, University of California Irvine, School of Medicine, Irvine, CA 92697.
  • Tafoya C; BSL-3 Laboratories, High Containment Core Facility, School of Medicine, University of California, Irvine.
  • Hitchcock L; BSL-3 Laboratories, High Containment Core Facility, School of Medicine, University of California, Irvine.
  • Landucci G; BSL-3 Laboratories, High Containment Core Facility, School of Medicine, University of California, Irvine.
  • Forthal DN; BSL-3 Laboratories, High Containment Core Facility, School of Medicine, University of California, Irvine.
  • El Babsiri A; BSL-3 Laboratories, High Containment Core Facility, School of Medicine, University of California, Irvine.
  • Tifrea DF; Division of Infectious Diseases, Department of Medicine, University of California, Irvine School of Medicine, Irvine, CA, USA.
  • Figueroa CJ; Laboratory of Cellular and Molecular Immunology, Gavin Herbert Eye Institute, University of California Irvine, School of Medicine, Irvine, CA 92697.
  • Nesburn AB; Department of Pathology and Laboratory Medicine, School of Medicine, Irvine, CA 92697.
  • Kuppermann BD; Department of Surgery, Divisions of Trauma, Burns & Critical Care, School of Medicine, Irvine, CA 92697.
  • Gil D; Laboratory of Cellular and Molecular Immunology, Gavin Herbert Eye Institute, University of California Irvine, School of Medicine, Irvine, CA 92697.
  • Jones TM; Laboratory of Cellular and Molecular Immunology, Gavin Herbert Eye Institute, University of California Irvine, School of Medicine, Irvine, CA 92697.
  • Ulmer JB; Department of Vaccines and Immunotherapies, TechImmune, LLC, University Lab Partners, Irvine, CA 92660, USA.
  • BenMohamed L; Department of Vaccines and Immunotherapies, TechImmune, LLC, University Lab Partners, Irvine, CA 92660, USA.
bioRxiv ; 2024 Feb 15.
Article in En | MEDLINE | ID: mdl-38405942
ABSTRACT
The first-generation Spike-alone-based COVID-19 vaccines have successfully contributed to reducing the risk of hospitalization, serious illness, and death caused by SARS-CoV-2 infections. However, waning immunity induced by these vaccines failed to prevent immune escape by many variants of concern (VOCs) that emerged from 2020 to 2024, resulting in a prolonged COVID-19 pandemic. We hypothesize that a next-generation Coronavirus (CoV) vaccine incorporating highly conserved non-Spike SARS-CoV-2 antigens would confer stronger and broader cross-protective immunity against multiple VOCs. In the present study, we identified ten non-Spike antigens that are highly conserved in 8.7 million SARS-CoV-2 strains, twenty-one VOCs, SARS-CoV, MERS-CoV, Common Cold CoVs, and animal CoVs. Seven of the 10 antigens were preferentially recognized by CD8+ and CD4+ T-cells from unvaccinated asymptomatic COVID-19 patients, irrespective of VOC infection. Three out of the seven conserved non-Spike T cell antigens belong to the early expressed Replication and Transcription Complex (RTC) region, when administered to the golden Syrian hamsters, in combination with Spike, as nucleoside-modified mRNA encapsulated in lipid nanoparticles (LNP) (i.e., combined mRNA/LNP-based pan-CoV vaccine) (i) Induced high frequencies of lung-resident antigen-specific CXCR5+CD4+ T follicular helper (TFH) cells, GzmB+CD4+ and GzmB+CD8+ cytotoxic T cells (TCYT), and CD69+IFN-γ+TNFα+CD4+ and CD69+IFN-γ+TNFα+CD8+ effector T cells (TEFF); and (ii) Reduced viral load and COVID-19-like symptoms caused by various VOCs, including the highly pathogenic B.1.617.2 Delta variant and the highly transmittable heavily Spike-mutated XBB1.5 Omicron sub-variant. The combined mRNA/LNP-based pan-CoV vaccine could be rapidly adapted for clinical use to confer broader cross-protective immunity against emerging highly mutated and pathogenic VOCs.
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Full text: 1 Collection: 01-internacional Database: MEDLINE Language: En Journal: BioRxiv Year: 2024 Document type: Article Country of publication: United States
Fulltext
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Full text: 1 Collection: 01-internacional Database: MEDLINE Language: En Journal: BioRxiv Year: 2024 Document type: Article Country of publication: United States