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

• Published in: Nature medicine Vol. 26; no. 11; pp. 1694 - 1700
• Main Authors: 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.
• Format: Journal Article
• Language: English
• Published: New York Nature Publishing Group US 01.11.2020; Nature Publishing Group
• Subjects: 631/326/590; 631/326/596/4130; Adenoviridae - genetics; Adenoviridae - immunology; Adenoviruses; Animals; Antibodies; Antibodies, Neutralizing - genetics; Antibodies, Neutralizing - therapeutic use; Biomedical and Life Sciences; Biomedicine; Cancer Research; Coronaviruses; COVID-19; COVID-19 - mortality; COVID-19 - pathology; COVID-19 - prevention & control; COVID-19 - virology; COVID-19 Vaccines - genetics; COVID-19 Vaccines - therapeutic use; Cricetinae; Disease Models, Animal; Female; Genetic Vectors; Hamsters; Humans; Immunization; Infectious Diseases; Letter; Male; Mesocricetus; Metabolic Diseases; Molecular Medicine; Mortality; Neurosciences; Pathogenesis; Pneumonia; Proteins; Replication; Respiratory diseases; Respiratory failure; Respiratory tract; SARS-CoV-2 - genetics; SARS-CoV-2 - immunology; Severe acute respiratory syndrome coronavirus 2; Severity of Illness Index; Spike Glycoprotein, Coronavirus - genetics; Spike Glycoprotein, Coronavirus - immunology; Spike protein; Vaccines; Vaccines, Synthetic - genetics; Vaccines, Synthetic - therapeutic use; Viral diseases; Viral Load; Weight loss; United States
• ISSN: 1078-8956; 1546-170X; 1546-170X
• DOI: 10.1038/s41591-020-1070-6

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. A single immunization with an adenovirus vector-based vaccine expressing a stabilized SARS-CoV-2 spike protein induces protection against SARS-CoV-2-induced weight loss, pneumonia and mortality in hamsters.