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

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

Coronavirus disease 2019 (COVID-19) in humans is often a clinically mild illness, but some individuals develop severe pneumonia, respiratory failure and death(1–4). Studies of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infection in hamsters(5–7) and nonhuman primates(8–10) 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 primates(11–13). 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.