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.
| العنوان: | 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. |
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| المؤلفون: | 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.; Department of Vaccines and Immunotherapies, TechImmune, LLC, University Lab Partners, Irvine, CA 92660, USA., Coulon PG; Laboratory of Cellular and Molecular Immunology, Gavin Herbert Eye Institute, University of California Irvine, School of Medicine, Irvine, CA 92697., Ibraim IC; BSL-3 Laboratories, High Containment Core Facility, School of Medicine, University of California, Irvine., 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.; Division of Infectious Diseases, Department of Medicine, University of California, Irvine School of Medicine, Irvine, CA, USA., El Babsiri A; Laboratory of Cellular and Molecular Immunology, Gavin Herbert Eye Institute, University of California Irvine, School of Medicine, Irvine, CA 92697., Tifrea DF; Department of Pathology and Laboratory Medicine, School of Medicine, Irvine, CA 92697., Figueroa CJ; Department of Surgery, Divisions of Trauma, Burns & Critical Care, School of Medicine, Irvine, CA 92697., Nesburn AB; Laboratory of Cellular and Molecular Immunology, Gavin Herbert Eye Institute, University of California Irvine, School of Medicine, Irvine, CA 92697., Kuppermann BD; Laboratory of Cellular and Molecular Immunology, Gavin Herbert Eye Institute, University of California Irvine, School of Medicine, Irvine, CA 92697., Gil D; Department of Vaccines and Immunotherapies, TechImmune, LLC, University Lab Partners, Irvine, CA 92660, USA., Jones TM; Department of Vaccines and Immunotherapies, TechImmune, LLC, University Lab Partners, Irvine, CA 92660, USA., Ulmer JB; Department of Vaccines and Immunotherapies, TechImmune, LLC, University Lab Partners, Irvine, CA 92660, USA., BenMohamed L; Laboratory of Cellular and Molecular Immunology, Gavin Herbert Eye Institute, University of California Irvine, School of Medicine, Irvine, CA 92697.; Institute for Immunology; University of California Irvine, School of Medicine, Irvine, CA 92697.; Department of Vaccines and Immunotherapies, TechImmune, LLC, University Lab Partners, Irvine, CA 92660, USA. |
| المصدر: | BioRxiv : the preprint server for biology [bioRxiv] 2024 Feb 15. Date of Electronic Publication: 2024 Feb 15. |
| نوع المنشور: | Preprint |
| اللغة: | English |
| بيانات الدورية: | Country of Publication: United States NLM ID: 101680187 Publication Model: Electronic Cited Medium: Internet NLM ISO Abbreviation: bioRxiv Subsets: PubMed not MEDLINE |
| مستخلص: | 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 (T Competing Interests: These studies were supported in part by Public Health Service Research grants AI158060, AI150091, AI143348, AI147499, AI143326, AI138764, AI124911, and AI110902 from the National Institutes of Allergy and Infectious Diseases (NIAID) to LBM and by R43AI174383 to TechImmune, LLC. LBM has an equity interest in TechImmune, LLC., a company that may potentially benefit from the research results and serves on the company's Scientific Advisory Board. LBM's relationship with TechImmune, LLC., has been reviewed and approved by the University of California, Irvine by its conflict-of-interest policies.Studies of this report were supported by Public Health Service Research grants AI158060, AI150091, AI143348, AI147499, AI143326, AI138764, AI124911, and AI110902 from the National Institutes of Allergy and Infectious Diseases (NIAID) to LBM. LBM has an equity interest in TechImmune, LLC., a company that may potentially benefit from the research results and serves on the company's Scientific Advisory Board. LBM's relationship with TechImmune, LLC., has been reviewed and approved by the University of California, Irvine by its conflict-of-interest policies. |
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| معلومات مُعتمدة: | R41 AI138764 United States AI NIAID NIH HHS; R01 AI143348 United States AI NIAID NIH HHS; R43 AI174383 United States AI NIAID NIH HHS; R01 AI158060 United States AI NIAID NIH HHS; R43 AI124911 United States AI NIAID NIH HHS; R01 AI150091 United States AI NIAID NIH HHS; R21 AI143326 United States AI NIAID NIH HHS; R21 AI110902 United States AI NIAID NIH HHS; R21 AI147499 United States AI NIAID NIH HHS |
| فهرسة مساهمة: | Keywords: CD4+ T cells; CD8+ T cells; COVID-19; Cross-protective; SARS-CoV-2; Variants of concern; pan-Coronavirus vaccine |
| تواريخ الأحداث: | Date Created: 20240226 Latest Revision: 20240229 |
| رمز التحديث: | 20240229 |
| مُعرف محوري في PubMed: | PMC10888826 |
| DOI: | 10.1101/2024.02.14.580225 |
| PMID: | 38405942 |
| قاعدة البيانات: | MEDLINE |
| DOI: | 10.1101/2024.02.14.580225 |
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