RT Journal Article
SR Electronic
T1 Single-dose respiratory mucosal delivery of next-generation viral-vectored COVID-19 vaccine provides robust protection against both ancestral and variant strains of SARS-CoV-2
JF bioRxiv
FD Cold Spring Harbor Laboratory
SP 2021.07.16.452721
DO 10.1101/2021.07.16.452721
A1 Sam Afkhami
A1 Michael R. D’Agostino
A1 Ali Zhang
A1 Hannah D. Stacey
A1 Art Marzok
A1 Alisha Kang
A1 Ramandeep Singh
A1 Jegarubee Bavananthasivam
A1 Gluke Ye
A1 Xiangqian Luo
A1 Fuan Wang
A1 Jann C. Ang
A1 Anna Zganiacz
A1 Uma Sankar
A1 Natallia Kazhdan
A1 Joshua F. E. Koenig
A1 Allyssa Phelps
A1 Manel Jordana
A1 Yonghong Wan
A1 Karen L. Mossman
A1 Mangalakumari Jeyanathan
A1 Amy Gillgrass
A1 Maria Fe C. Medina
A1 Fiona Smaill
A1 Brian D. Lichty
A1 Matthew S. Miller
A1 Zhou Xing
YR 2021
UL http://biorxiv.org/content/early/2021/07/19/2021.07.16.452721.abstract
AB The emerging SARS-CoV-2 variants of concern (VOC) increasingly threaten the effectiveness of current first-generation COVID-19 vaccines that are administered intramuscularly and are designed to only target the spike protein. There is thus a pressing need to develop next-generation vaccine strategies to provide more broad and long-lasting protection. By using adenoviral vectors (Ad) of human and chimpanzee origin, we developed Ad-vectored trivalent COVID-19 vaccines expressing Spike-1, Nucleocapsid and RdRp antigens and evaluated them following single-dose intramuscular or intranasal immunization in murine models. We show that respiratory mucosal immunization, particularly with chimpanzee Ad-vectored vaccine, is superior to intramuscular immunization in induction of the three-arm immunity, consisting of local and systemic antibody responses, mucosal tissue-resident memory T cells, and mucosal trained innate immunity. We further show that single-dose intranasal immunization provides robust protection against not only the ancestral strain of SARS-CoV-2, but also two emerging VOC, B.1.1.7 and B.1.351. Our findings indicate that single-dose respiratory mucosal delivery of an Ad-vectored multivalent vaccine represents an effective next-generation COVID-19 vaccine strategy against current and future VOC. This strategy has great potential to be used not only to boost first-generation vaccine-induced immunity but also to expand the breadth of protective T cell immunity at the respiratory mucosa.Competing Interest StatementThe authors have declared no competing interest.