1. Ad26 vaccine protects against SARS-CoV-2 severe clinical disease in hamsters.
- Author
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Tostanoski LH, Wegmann F, Martinot AJ, Loos C, McMahan K, Mercado NB, Yu J, Chan CN, Bondoc S, Starke CE, Nekorchuk M, Busman-Sahay K, Piedra-Mora C, Wrijil LM, Ducat S, Custers J, Atyeo C, Fischinger S, Burke JS, Feldman J, Hauser BM, Caradonna TM, Bondzie EA, Dagotto G, Gebre MS, Jacob-Dolan C, Lin Z, Mahrokhian SH, Nampanya F, Nityanandam R, Pessaint L, Porto M, Ali V, Benetiene D, Tevi K, Andersen H, Lewis MG, Schmidt AG, Lauffenburger DA, Alter G, Estes JD, Schuitemaker H, Zahn R, and Barouch DH
- Subjects
- Adenoviridae immunology, Animals, Antibodies, Neutralizing genetics, Antibodies, Neutralizing therapeutic use, COVID-19 mortality, COVID-19 pathology, COVID-19 virology, COVID-19 Vaccines genetics, Cricetinae, Disease Models, Animal, Female, Genetic Vectors, Humans, Male, Mesocricetus, SARS-CoV-2 genetics, Severity of Illness Index, Vaccines, Synthetic genetics, Vaccines, Synthetic therapeutic use, Viral Load, Adenoviridae genetics, COVID-19 prevention & control, COVID-19 Vaccines therapeutic use, SARS-CoV-2 immunology, Spike Glycoprotein, Coronavirus genetics, Spike Glycoprotein, Coronavirus immunology
- Abstract
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 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.- Published
- 2020
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