Journal
CELL
Volume 185, Issue 5, Pages 896-+Publisher
CELL PRESS
DOI: 10.1016/j.cell.2022.02.005
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Funding
- Canadian Institutes of Health Research (CIHR) COVID-19 Rapid Research Project
- Innovative Research Program of National Sanitarium Association of Canada
- CIHR New Investigator Award
- Ontario Early Research Award
- Canada Research Chair (Tier 2) in Viral Pandemics
- CIHR Canada Graduate Scholarship Doctoral Award
- Physicians' Services Incorporated Research Trainee Fellowship
- Ontario Graduate Scholarship
- Canadian Society for Virology United Supermarket Studentship
- Canadian Foundation for Innovation
- CIHR Foundation Program
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The study found that using adenoviral vectors with a multivalent vaccine through intranasal immunization can generate better mucosal immune responses, including local and systemic antibody responses, mucosal tissue-resident memory T cells, and mucosal trained innate immunity, and provide protection against multiple viral variants.
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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