1. Respiratory mucosal delivery of next-generation COVID-19 vaccine provides robust protection against both ancestral and variant strains of SARS-CoV-2.
- Author
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Afkhami S, D'Agostino MR, Zhang A, Stacey HD, Marzok A, Kang A, Singh R, Bavananthasivam J, Ye G, Luo X, Wang F, Ang JC, Zganiacz A, Sankar U, Kazhdan N, Koenig JFE, Phelps A, Gameiro SF, Tang S, Jordana M, Wan Y, Mossman KL, Jeyanathan M, Gillgrass A, Medina MFC, Smaill F, Lichty BD, Miller MS, and Xing Z
- Subjects
- Administration, Intranasal, Animals, Antibodies, Viral blood, Antibodies, Viral immunology, B-Lymphocytes immunology, B-Lymphocytes metabolism, COVID-19 virology, COVID-19 Vaccines immunology, Cytokines blood, Genetic Vectors genetics, Genetic Vectors immunology, Genetic Vectors metabolism, Mice, Mice, Inbred BALB C, Mice, Inbred C57BL, Neutralization Tests, Nucleocapsid genetics, Nucleocapsid immunology, Nucleocapsid metabolism, Pan troglodytes, SARS-CoV-2 genetics, SARS-CoV-2 immunology, SARS-CoV-2 isolation & purification, Spike Glycoprotein, Coronavirus genetics, Spike Glycoprotein, Coronavirus immunology, Spike Glycoprotein, Coronavirus metabolism, T-Lymphocytes immunology, T-Lymphocytes metabolism, COVID-19 prevention & control, COVID-19 Vaccines administration & dosage, Immunity, Mucosal
- Abstract
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., Competing Interests: Declaration of interests B.D.L., F.S., and Z.X. are inventors on a US provisional patent application no. 63/222723, entitled “Novel COVID vaccine and method for delivery.” All other authors declare no competing interests., (Copyright © 2022 The Author(s). Published by Elsevier Inc. All rights reserved.)
- Published
- 2022
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