@article{6e233dc62254492c8ca47d2b99a5c490,
title = "A single intranasal or intramuscular immunization with chimpanzee adenovirus-vectored SARS-CoV-2 vaccine protects against pneumonia in hamsters",
abstract = "The development of an effective vaccine against severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), the etiologic agent of coronavirus disease 2019 (COVID-19), is a global priority. Here, we compare the protective capacity of intranasal and intramuscular delivery of a chimpanzee adenovirus-vectored vaccine encoding a prefusion stabilized spike protein (chimpanzee adenovirus [ChAd]-SARS-CoV-2-S) in Golden Syrian hamsters. Although immunization with ChAd-SARS-CoV-2-S induces robust spike-protein-specific antibodies capable of neutralizing the virus, antibody levels in serum are higher in hamsters vaccinated by an intranasal compared to intramuscular route. Accordingly, against challenge with SARS-CoV-2, ChAd-SARS-CoV-2-S-immunized hamsters are protected against less weight loss and have reduced viral infection in nasal swabs and lungs, and reduced pathology and inflammatory gene expression in the lungs, compared to ChAd-control immunized hamsters. Intranasal immunization with ChAd-SARS-CoV-2-S provides superior protection against SARS-CoV-2 infection and inflammation in the upper respiratory tract. These findings support intranasal administration of the ChAd-SARS-CoV-2-S candidate vaccine to prevent SARS-CoV-2 infection, disease, and possibly transmission.",
keywords = "ChAd vectored vaccine, SARS-CoV-2, Syrian hamster, intranasal immunization",
author = "Bricker, {Traci L.} and Darling, {Tamarand L.} and Hassan, {Ahmed O.} and Harastani, {Houda H.} and Allison Soung and Xiaoping Jiang and Dai, {Ya Nan} and Haiyan Zhao and Adams, {Lucas J.} and Holtzman, {Michael J.} and Bailey, {Adam L.} and Case, {James Brett} and Fremont, {Daved H.} and Robyn Klein and Diamond, {Michael S.} and Boon, {Adrianus C.M.}",
note = "Funding Information: We acknowledge Krzysztof Hyrc for help with the Hamamatsu NanoZoomer slide scanning system. We also thank Amy Dillard for help with the serum collections from the animals and Ali Ellebedy and Jackson Turner for help with antibody ELISA and recombinant protein. We thank Drs. Susan Cook and Ken Boschert for support of the COVID-19 research. This study was funded by NIH contracts and grants (R01 AI157155, 75N93019C00062, U01 AI151810, HHSN272201400018C, and HHSN272201700060C). J.B.C. is supported by a Helen Hay Whitney Foundation postdoctoral fellowship. T.L.B. and T.L.D. performed the animal experiments. A.O.H. upscaled and purified the ChAd vectors. A.O.H. A.C.M.B. and J.B.C. performed the serological analysis. H.H.H. T.L.B. and T.L.D. performed viral load analysis by qRT-PCR, focus forming, or plaque assay. T.L.D. developed and validated primer-probes sets for Syrian hamster genes and performed the host gene expression assays. M.J.H. performed the histology analysis. A.S. X.J. and R.K. performed the histology and RNA-ISH on the hamster heads. A.C.M.B. performed RNA-ISH on the hamster lungs. A.L.B. and J.B.C. provided qPCR reagents and protocols. Y.-N.D. H.Z. L.J.A. and D.H.F. provided recombinant proteins for serological analysis. M.S.D. and A.C.M.B. provided supervision and acquired funding. A.C.M.B. wrote the initial draft, with the other authors providing editorial comments. M.S.D. is a consultant for Inbios, Vir Biotechnology, NGM Biopharmaceuticals, 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. The Boon laboratory has received unrelated funding support in sponsored research agreements from AI Therapeutics, GreenLight Biosciences Inc. AbbVie Inc. and Nano targeting & Therapy Biopharma Inc. M.S.D. and A.O.H. have filed a disclosure with Washington University for possible commercial development of ChAd-SARS-CoV-2. A.C.M.B. is a recipient of a licensing agreement with Abbvie Inc. for commercial development of SARS-CoV-2 monoclonal antibody (mAb). Funding Information: We acknowledge Krzysztof Hyrc for help with the Hamamatsu NanoZoomer slide scanning system. We also thank Amy Dillard for help with the serum collections from the animals and Ali Ellebedy and Jackson Turner for help with antibody ELISA and recombinant protein. We thank Drs. Susan Cook and Ken Boschert for support of the COVID-19 research. This study was funded by NIH contracts and grants ( R01 AI157155 , 75N93019C00062 , U01 AI151810 , HHSN272201400018C , and HHSN272201700060C ). J.B.C. is supported by a Helen Hay Whitney Foundation postdoctoral fellowship. Publisher Copyright: {\textcopyright} 2021 The Author(s)",
year = "2021",
month = jul,
day = "20",
doi = "10.1016/j.celrep.2021.109400",
language = "English",
volume = "36",
journal = "Cell Reports",
issn = "2211-1247",
number = "3",
}