Authors
Sam Afkhami, Michael R D’Agostino, Ali Zhang, Hannah D Stacey, Art Marzok, Alisha Kang, Ramandeep Singh, Jegarubee Bavananthasivam, Gluke Ye, Xiangqian Luo, Fuan Wang, Jann C Ang, Anna Zganiacz, Uma Sankar, Natallia Kazhdan, Joshua FE Koenig, Allyssa Phelps, Steven F Gameiro, Shangguo Tang, Manel Jordana, Yonghong Wan, Karen L Mossman, Mangalakumari Jeyanathan, Amy Gillgrass, Maria Fe C Medina, Fiona Smaill, Brian D Lichty, Matthew S Miller, Zhou Xing
Publication date
2022/3/3
Journal
Cell
Volume
185
Issue
5
Pages
896-915. e19
Publisher
Elsevier
Description
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 …
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