@article{fdd91cea71414d33a349e3e977e01a33,
title = "A Single-Dose Intranasal ChAd Vaccine Protects Upper and Lower Respiratory Tracts against SARS-CoV-2",
abstract = "The coronavirus disease 2019 pandemic has made deployment of an effective vaccine a global health priority. We evaluated the protective activity of a chimpanzee adenovirus-vectored vaccine encoding a prefusion stabilized spike protein (ChAd-SARS-CoV-2-S) in challenge studies with severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) and mice expressing the human angiotensin-converting enzyme 2 receptor. Intramuscular dosing of ChAd-SARS-CoV-2-S induces robust systemic humoral and cell-mediated immune responses and protects against lung infection, inflammation, and pathology but does not confer sterilizing immunity, as evidenced by detection of viral RNA and induction of anti-nucleoprotein antibodies after SARS-CoV-2 challenge. In contrast, a single intranasal dose of ChAd-SARS-CoV-2-S induces high levels of neutralizing antibodies, promotes systemic and mucosal immunoglobulin A (IgA) and T cell responses, and almost entirely prevents SARS-CoV-2 infection in both the upper and lower respiratory tracts. Intranasal administration of ChAd-SARS-CoV-2-S is a candidate for preventing SARS-CoV-2 infection and transmission and curtailing pandemic spread.",
keywords = "COVID-19, IgA, SARS-CoV-2, T cells, antibody, intranasal, mucosal immunity, pathogenesis, protection, vaccine",
author = "Hassan, {Ahmed O.} and Kafai, {Natasha M.} and Dmitriev, {Igor P.} and Fox, {Julie M.} and Smith, {Brittany K.} and Harvey, {Ian B.} and Chen, {Rita E.} and Winkler, {Emma S.} and Wessel, {Alex W.} and Case, {James Brett} and Elena Kashentseva and McCune, {Broc T.} and Bailey, {Adam L.} and Haiyan Zhao and VanBlargan, {Laura A.} and Dai, {Ya Nan} and Meisheng Ma and Adams, {Lucas J.} and Swathi Shrihari and Danis, {Jonathan E.} and Gralinski, {Lisa E.} and Hou, {Yixuan J.} and Alexandra Sch{\"a}fer and Kim, {Arthur S.} and Keeler, {Shamus P.} and Daniela Weiskopf and Baric, {Ralph S.} and Holtzman, {Michael J.} and Fremont, {Daved H.} and Curiel, {David T.} and Diamond, {Michael S.}",
note = "Funding Information: This study was supported by NIH contracts and grants (75N93019C00062, 75N9301900065, R01 AI127828, R01 AI130591, R01 AI149644, and R35 HL145242), Center for Structural Genomics of Infectious Diseases (HHSN272201400018C, and HHSN272201200026C), and the Defense Advanced Research Projects Agency (HR001117S0019). B.T.M. is supported by F32 AI138392, E.S.W. is supported by T32 AI007163, and J.B.C. is supported by a Helen Hay Whitney Foundation postdoctoral fellowship. We thank Sean Whelan, Susan Cook, and Jennifer Philips for facilitating studies with SARS-CoV-2; James Earnest for performing cell culture; and the Pulmonary Morphology Core at Washington University School of Medicine for tissue sectioning. Some figures were created with BioRender software. A.O.H. designed experiments and performed intranasal inoculations of adenovirus. I.P.D. E.K. A.O.H. and D.T.C. designed and generated the ChAd constructs. J.B.C. propagated the SARS-CoV-2 stocks and performed plaque assays. A.L.B. designed the qRT-PCR assays. A.O.H. evaluated cell-mediated immune responses. A.O.H. N.M.K. E.S.W. S.S. B.T.M. R.E.C. L.E.G. and J.M.F. performed clinical analysis, histopathological studies, and viral burden analyses. B.T.M. performed in situ hybridization. A.S. and Y.J.H. designed and performed experiments with recombinant strains of SARS-CoV-2. A.S.K. performed flow cytometry analysis experiments. S.P.K. and M.J.H. analyzed the tissue sections for histopathology. A.W.W. performed the ChAd-immune serum neutralization assays. D.W. generated the T cell peptide pools. L.A.V.B. provided SARS-CoV-2 monoclonal antibodies. H.Z. Y.-N.D. M.M. L.J.A. and D.H.F. designed and produced the recombinant S, RBD, and N proteins. I.B.H. J.E.D. and B.K.S. performed ELISAs, and J.B.C. and R.E.C. performed neutralization assays. R.S.B. designed experiments and secured funding. A.O.H. 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, and NGM Biopharmaceuticals and on the Scientific Advisory Board of Moderna. The Diamond laboratory has received unrelated funding support from Moderna, Vir Biotechnology, and Emergent BioSolutions. M.S.D. D.T.C. A.O.H. and I.P.D. have filed a disclosure with Washington University for possible development of ChAd-SARS-CoV-2. M.J.H. is a member of the DSMB for AstraZeneca and founder of NuPeak Therapeutics. The Baric laboratory has received unrelated funding support from Takeda, Pfizer, and Eli Lilly. Funding Information: M.S.D. is a consultant for Inbios, Vir Biotechnology, and NGM Biopharmaceuticals and on the Scientific Advisory Board of Moderna. The Diamond laboratory has received unrelated funding support from Moderna, Vir Biotechnology, and Emergent BioSolutions. M.S.D., D.T.C., A.O.H., and I.P.D. have filed a disclosure with Washington University for possible development of ChAd-SARS-CoV-2. M.J.H. is a member of the DSMB for AstraZeneca and founder of NuPeak Therapeutics. The Baric laboratory has received unrelated funding support from Takeda, Pfizer, and Eli Lilly. Funding Information: This study was supported by NIH contracts and grants ( 75N93019C00062 , 75N9301900065 , R01 AI127828 , R01 AI130591 , R01 AI149644 , and R35 HL145242 ), Center for Structural Genomics of Infectious Diseases ( HHSN272201400018C , and HHSN272201200026C ), and the Defense Advanced Research Projects Agency ( HR001117S0019 ). B.T.M. is supported by F32 AI138392 , E.S.W. is supported by T32 AI007163 , and J.B.C. is supported by a Helen Hay Whitney Foundation postdoctoral fellowship. We thank Sean Whelan, Susan Cook, and Jennifer Philips for facilitating studies with SARS-CoV-2; James Earnest for performing cell culture; and the Pulmonary Morphology Core at Washington University School of Medicine for tissue sectioning. Some figures were created with BioRender software. Publisher Copyright: {\textcopyright} 2020 Elsevier Inc.",
year = "2020",
month = oct,
day = "1",
doi = "10.1016/j.cell.2020.08.026",
language = "English",
volume = "183",
pages = "169--184.e13",
journal = "Cell",
issn = "0092-8674",
number = "1",
}