• Lisa H Tostanoski, Frank Wegmann, Amanda J Martinot, Carolin Loos, Katherine McMahan, Noe B Mercado, Jingyou Yu, Chi N Chan, Stephen Bondoc, Carly E Starke, Michael Nekorchuk, Kathleen Busman-Sahay, Cesar Piedra-Mora, Linda M Wrijil, Sarah Ducat, Jerome Custers, Caroline Atyeo, Stephanie Fischinger, John S Burke, Jared Feldman, Blake M Hauser, Timothy M Caradonna, Esther A Bondzie, Gabriel Dagotto, Makda S Gebre, Catherine Jacob-Dolan, Zijin Lin, Shant H Mahrokhian, Felix Nampanya, Ramya Nityanandam, Laurent Pessaint, Maciel Porto, Vaneesha Ali, Dalia Benetiene, Komlan Tevi, Hanne Andersen, Mark G Lewis, Aaron G Schmidt, Douglas A Lauffenburger, Galit Alter, Jacob D Estes, Hanneke Schuitemaker, Roland Zahn, and Dan H Barouch.
• Center for Virology and Vaccine Research, Beth Israel Deaconess Medical Center, Harvard Medical School, Boston, MA, USA.
• Nat. Med. 2020 Nov 1; 26 (11): 1694-1700.

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.

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