@article{b2dea4a3719346409db295bca7b5fc1e,
title = "An intranasal vaccine durably protects against SARS-CoV-2 variants in mice",
abstract = "SARS-CoV-2 variants that attenuate antibody neutralization could jeopardize vaccine efficacy. We recently reported the protective activity of an intranasally administered spike protein-based chimpanzee adenovirus-vectored vaccine (ChAd-SARS-CoV-2-S) in animals, which has advanced to human trials. Here, we assessed its durability, dose response, and cross-protective activity in mice. A single intranasal dose of ChAd-SARS-CoV-2-S induced durably high neutralizing and Fc effector antibody responses in serum and S-specific IgG and IgA secreting long-lived plasma cells in the bone marrow. Protection against a historical SARS-CoV-2 strain was observed across a 100-fold vaccine dose range and over a 200-day period. At 6 weeks or 9 months after vaccination, serum antibodies neutralized SARS-CoV-2 strains with B.1.351, B.1.1.28, and B.1.617.1 spike proteins and conferred almost complete protection in the upper and lower respiratory tracts after challenge with variant viruses. Thus, in mice, intranasal immunization with ChAd-SARS-CoV-2-S provides durable protection against historical and emerging SARS-CoV-2 strains.",
keywords = "COVID-19, SARS-CoV-2, antibody, durability, mice, mucosal immunity, pathogenesis, vaccine, variants of concern",
author = "Hassan, {Ahmed O.} and Swathi Shrihari and Gorman, {Matthew J.} and Baoling Ying and Dansu Yaun and Saravanan Raju and Chen, {Rita E.} and Dmitriev, {Igor P.} and Elena Kashentseva and Adams, {Lucas J.} and Colin Mann and Davis-Gardner, {Meredith E.} and Suthar, {Mehul S.} and Shi, {Pei Yong} and Saphire, {Erica Ollmann} and Fremont, {Daved H.} and Curiel, {David T.} and Galit Alter and Diamond, {Michael S.}",
note = "Funding Information: This study was supported by NIH contracts and grants (R01 AI157155, R01 EB026468-02S1, 75N93019C00062, 75N93021C00017, HHSN272201400018C, and U19 142790) and INV-00613 from the Bill and Melinda Gates Foundation. This work also was supported by Woodruff Health Sciences Center 2020 COVID-19 CURE Award. A.O.H. I.P.D. and E.K. generated the vaccines. A.O.H. performed ELISA assays and analyzed the data. A.O.H. performed neutralization assays. S.R. performed ELISPOT assays. M.J.G. D.Y. and G.A. designed and/or performed the binding and Fc effector function experiments. L.J.A. D.H.F. C.M. and E.O.S. designed and produced the recombinant S and RBD proteins and antibodies. A.O.H. S.S. and B.Y. performed and evaluated the virological assays. P.-Y.S. M.E.D.-G. and M.S.S. provided key reagents. M.S.D. D.H.F. G.A. and D.T.C. designed experiments and secured funding. A.O.H. M.J.G. and M.S.D. wrote the initial draft, with the other authors providing editorial comments. M.S.D. is a consultant for Inbios, Vir Biotechnology, Fotress Biotech, and Carnival Corporation and on the Scientific Advisory Board of Moderna and Immunome. The Diamond laboratory has received unrelated funding support in sponsored research agreements from Moderna, Vir Biotechnology, and Emergent BioSolutions. M.S.D. is on the Advisory Board of Moderna. M.S.D. I.P.D. D.T.C. and A.O.H. have filed a disclosure with Washington University for possible commercial development of ChAd-SARS-CoV-2-S. D.T.C. is an equity holder in Precision Virologics, Inc. which has optioned the ChAd-SARS-CoV-2-S vaccine. Funding Information: This study was supported by NIH contracts and grants ( R01 AI157155 , R01 EB026468-02S1 , 75N93019C00062 , 75N93021C00017 , HHSN272201400018C , and U19 142790 ) and INV-00613 from the Bill and Melinda Gates Foundation . This work also was supported by Woodruff Health Sciences Center 2020 COVID-19 CURE Award . Publisher Copyright: {\textcopyright} 2021 The Author(s)",
year = "2021",
month = jul,
day = "27",
doi = "10.1016/j.celrep.2021.109452",
language = "English",
volume = "36",
journal = "Cell Reports",
issn = "2211-1247",
number = "4",
}