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

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

doi:10.1038/s41591-020-1070-6

Abstract

Coronavirus 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.

Highlights

SARS-CoV-2 can infect nonhuman primates[8,9,10], hamsters[5,6,7], ferrets[14,15,16], hACE2 transgenic mice[17,18] and other species[16], but clinical disease in these models has generally been mild
A severe pneumonia model would be useful for preclinical evaluation of SARS-CoV-2 vaccines and other countermeasures, because SARS-CoV-2 infection in humans can lead to severe clinical disease, respiratory failure and mortality[1,2,3,4]
In the high-dose group, four animals were necropsied on day 2, four animals were necropsied on day 4 for tissue viral loads and histopathology and the remaining eight animals were followed longitudinally

Summary

Introduction

SARS-CoV-2 can infect nonhuman primates[8,9,10], hamsters[5,6,7], ferrets[14,15,16], hACE2 transgenic mice[17,18] and other species[16], but clinical disease in these models has generally been mild. These data demonstrate that high-dose SARS-CoV-2 infection in hamsters led to severe weight loss and partial mortality. Hamsters infected with high-dose SARS-CoV-2 were assessed by histopathology on days 2 (n = 4), 4 (n = 4), 6–7 (n = 6) and 14 (n = 2).

Results

Conclusion