Ad26 vaccine protects against SARS-CoV-2 severe clinical disease in hamsters

Author:

Tostanoski Lisa H.ORCID,Wegmann FrankORCID,Martinot Amanda J.ORCID,Loos CarolinORCID,McMahan Katherine,Mercado Noe B.ORCID,Yu Jingyou,Chan Chi N.ORCID,Bondoc Stephen,Starke Carly E.,Nekorchuk Michael,Busman-Sahay KathleenORCID,Piedra-Mora Cesar,Wrijil Linda M.ORCID,Ducat SarahORCID,Custers Jerome,Atyeo Caroline,Fischinger StephanieORCID,Burke John S.ORCID,Feldman Jared,Hauser Blake M.ORCID,Caradonna Timothy M.,Bondzie Esther A.,Dagotto GabrielORCID,Gebre Makda S.,Jacob-Dolan CatherineORCID,Lin Zijin,Mahrokhian Shant H.ORCID,Nampanya Felix,Nityanandam Ramya,Pessaint Laurent,Porto Maciel,Ali Vaneesha,Benetiene Dalia,Tevi Komlan,Andersen HanneORCID,Lewis Mark G.,Schmidt Aaron G.,Lauffenburger Douglas A.ORCID,Alter GalitORCID,Estes Jacob D.,Schuitemaker Hanneke,Zahn RolandORCID,Barouch Dan H.ORCID

Abstract

AbstractCoronavirus disease 2019 (COVID-19) in humans is often a clinically mild illness, but some individuals develop severe pneumonia, respiratory failure and death1–4. Studies of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infection in hamsters5–7 and nonhuman primates8–10 have generally reported mild clinical disease, and preclinical SARS-CoV-2 vaccine studies have demonstrated reduction of viral replication in the upper and lower respiratory tracts in nonhuman primates11–13. Here we show that high-dose intranasal SARS-CoV-2 infection in hamsters results in severe clinical disease, including high levels of virus replication in tissues, extensive pneumonia, weight loss and mortality in a subset of animals. A single immunization with an adenovirus serotype 26 vector-based vaccine expressing a stabilized SARS-CoV-2 spike protein elicited binding and neutralizing antibody responses and protected against SARS-CoV-2-induced weight loss, pneumonia and mortality. These data demonstrate vaccine protection against SARS-CoV-2 clinical disease. This model should prove useful for preclinical studies of SARS-CoV-2 vaccines, therapeutics and pathogenesis.

Funder

Bill and Melinda Gates Foundation

U.S. Department of Health & Human Services | National Institutes of Health

Janssen Research and Development

Publisher

Springer Science and Business Media LLC

Subject

General Biochemistry, Genetics and Molecular Biology,General Medicine

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