Respiratory mucosal delivery of next-generation COVID-19 vaccine provides robust protection against both ancestral and variant strains of SARS-CoV-2
Sam AfkhamiMcMaster Immunology Research Centre, M.G. DeGroote Institute for Infectious Disease Research, Department of Medicine, McMaster University, Hamilton, ON L8S 4K1, CanadaMichael R. D’AgostinoMcMaster Immunology Research Centre, M. G. DeGroote Institute for Infectious Disease Research, Department of Biochemistry & Biomedical Sciences, McMaster University, Hamilton, ON L8S 4K1, CanadaAli ZhangMcMaster Immunology Research Centre, M. G. DeGroote Institute for Infectious Disease Research, Department of Biochemistry & Biomedical Sciences, McMaster University, Hamilton, ON L8S 4K1, CanadaHannah D. StaceyMcMaster Immunology Research Centre, M. G. DeGroote Institute for Infectious Disease Research, Department of Biochemistry & Biomedical Sciences, McMaster University, Hamilton, ON L8S 4K1, CanadaArt MarzokMcMaster Immunology Research Centre, M. G. DeGroote Institute for Infectious Disease Research, Department of Biochemistry & Biomedical Sciences, McMaster University, Hamilton, ON L8S 4K1, CanadaAlisha KangMcMaster Immunology Research Centre, M.G. DeGroote Institute for Infectious Disease Research, Department of Medicine, McMaster University, Hamilton, ON L8S 4K1, CanadaRamandeep SinghMcMaster Immunology Research Centre, M.G. DeGroote Institute for Infectious Disease Research, Department of Medicine, McMaster University, Hamilton, ON L8S 4K1, CanadaJegarubee BavananthasivamMcMaster Immunology Research Centre, M.G. DeGroote Institute for Infectious Disease Research, Department of Medicine, McMaster University, Hamilton, ON L8S 4K1, CanadaGluke YeMcMaster Immunology Research Centre, M.G. DeGroote Institute for Infectious Disease Research, Department of Medicine, McMaster University, Hamilton, ON L8S 4K1, CanadaXiang‐Qian LuoMcMaster Immunology Research Centre, M.G. DeGroote Institute for Infectious Disease Research, Department of Medicine, McMaster University, Hamilton, ON L8S 4K1, Canada; Department of Pediatric Otolaryngology, Shenzhen Hospital, Southern Medical University, Shenzhen, ChinaFuan WangMcMaster Immunology Research Centre, M.G. DeGroote Institute for Infectious Disease Research, Department of Medicine, McMaster University, Hamilton, ON L8S 4K1, CanadaJann C. AngMcMaster Immunology Research Centre, M. G. DeGroote Institute for Infectious Disease Research, Department of Biochemistry & Biomedical Sciences, McMaster University, Hamilton, ON L8S 4K1, CanadaAnna ZganiaczMcMaster Immunology Research Centre, M.G. DeGroote Institute for Infectious Disease Research, Department of Medicine, McMaster University, Hamilton, ON L8S 4K1, CanadaUma SankarMcMaster Immunology Research Centre, M.G. DeGroote Institute for Infectious Disease Research, Department of Medicine, McMaster University, Hamilton, ON L8S 4K1, CanadaNatallia KazhdanMcMaster Immunology Research Centre, M.G. DeGroote Institute for Infectious Disease Research, Department of Medicine, McMaster University, Hamilton, ON L8S 4K1, CanadaJoshua F. E. KoenigMcMaster Immunology Research Centre, M.G. DeGroote Institute for Infectious Disease Research, Department of Medicine, McMaster University, Hamilton, ON L8S 4K1, CanadaAllyssa PhelpsMcMaster Immunology Research Centre, M.G. DeGroote Institute for Infectious Disease Research, Department of Medicine, McMaster University, Hamilton, ON L8S 4K1, CanadaSteven F. GameiroMcMaster Immunology Research Centre, M.G. DeGroote Institute for Infectious Disease Research, Department of Medicine, McMaster University, Hamilton, ON L8S 4K1, CanadaShangguo TangDepartment of Pathology and Molecular Medicine, M.G. DeGroote Institute for Infectious Disease Research, McMaster University, Hamilton, ON L8S 4K1, CanadaManel JordanaMcMaster Immunology Research Centre, M.G. DeGroote Institute for Infectious Disease Research, Department of Medicine, McMaster University, Hamilton, ON L8S 4K1, CanadaYonghong WanMcMaster Immunology Research Centre, M.G. DeGroote Institute for Infectious Disease Research, Department of Medicine, McMaster University, Hamilton, ON L8S 4K1, CanadaKaren MossmanMcMaster Immunology Research Centre, M.G. DeGroote Institute for Infectious Disease Research, Department of Medicine, McMaster University, Hamilton, ON L8S 4K1, CanadaMangalakumari JeyanathanMcMaster Immunology Research Centre, M.G. DeGroote Institute for Infectious Disease Research, Department of Medicine, McMaster University, Hamilton, ON L8S 4K1, CanadaAmy GillgrassMcMaster Immunology Research Centre, M.G. DeGroote Institute for Infectious Disease Research, Department of Medicine, McMaster University, Hamilton, ON L8S 4K1, CanadaMaria Fe C. MedinaMcMaster Immunology Research Centre, M.G. DeGroote Institute for Infectious Disease Research, Department of Medicine, McMaster University, Hamilton, ON L8S 4K1, CanadaFiona SmaillDepartment of Pathology and Molecular Medicine, M.G. DeGroote Institute for Infectious Disease Research, McMaster University, Hamilton, ON L8S 4K1, CanadaBrian D. LichtyMcMaster Immunology Research Centre, M.G. DeGroote Institute for Infectious Disease Research, Department of Medicine, McMaster University, Hamilton, ON L8S 4K1, Canada. Electronic address: [email protected]Matthew S. MillerMcMaster Immunology Research Centre, M. G. DeGroote Institute for Infectious Disease Research, Department of Biochemistry & Biomedical Sciences, McMaster University, Hamilton, ON L8S 4K1, Canada. Electronic address: [email protected]Zhou XingMcMaster Immunology Research Centre, M.G. DeGroote Institute for Infectious Disease Research, Department of Medicine, McMaster University, Hamilton, ON L8S 4K1, Canada. Electronic address: [email protected]
2022en
ABI
Аннотация
The emerging SARS-CoV-2 variants of concern (VOCs) threaten the effectiveness of current COVID-19 vaccines administered intramuscularly and designed to only target the spike protein. There is a pressing need to develop next-generation vaccine strategies for broader and long-lasting protection. Using adenoviral vectors (Ad) of human and chimpanzee origin, we evaluated Ad-vectored trivalent COVID-19 vaccines expressing spike-1, nucleocapsid, and RdRp antigens in murine models. We show that single-dose intranasal immunization, particularly with chimpanzee Ad-vectored vaccine, is superior to intramuscular immunization in induction of the tripartite protective immunity consisting of local and systemic antibody responses, mucosal tissue-resident memory T cells and mucosal trained innate immunity. We further show that intranasal immunization provides protection against both the ancestral SARS-CoV-2 and two VOC, B.1.1.7 and B.1.351. Our findings indicate that respiratory mucosal delivery of Ad-vectored multivalent vaccine represents an effective next-generation COVID-19 vaccine strategy to induce all-around mucosal immunity against current and future VOC.
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