Most people with COVID-19 have relatively mild disease, but a subset of people develop severe pneumonia and respiratory failure, potentially leading to death. Beth Israel Deaconess Medical Centre (BIDMC) immunologist Dr Dan H Barouch, and colleagues showed in recently published previous work that a candidate COVID-19 vaccine raised neutralising antibodies that robustly protected non-human primates (NHPs) against SARS-CoV-2, the virus that causes COVID-19.
Now, in new research, Barouch and colleagues demonstrated that the optimal vaccine elicited robust immune response in Syrian golden hamsters and prevented severe clinical disease – including weight loss, pneumonia and death.
"We recently reported that an Ad26-based SARS-CoV-2 vaccine provided robust protection in rhesus macaques, and this vaccine is currently being evaluated in humans," said Barouch, who is director of BIDMC's Centre for Virology and Vaccine Research. "However, nonhuman primates typically don't get severe clinical disease, and thus it was important to study whether this vaccine could prevent severe pneumonia and death due to SARS-CoV-2 in hamsters, which are more susceptible to clinical disease."
The vaccine – developed through a collaboration between BIDMC and Johnson & Johnson (J&J) – uses a common cold virus, called adenovirus serotype 26 (Ad26), to deliver the SARS-CoV-2 spike protein into host cells, where it stimulates the body to raise immune responses against the coronavirus. Barouch's group and J&J developed a series of vaccine candidates designed to express different variants of the SARS-CoV-2 spike protein, which is the major target for neutralising antibodies.
In the current study, the researchers immunised Syrian golden hamsters with a single injection of the Ad26-based SARS-CoV-2 vaccine, which induced neutralizing antibodies in all animals. Four weeks later, the animals were exposed to a high dose of SARS-CoV-2. Vaccinated animals lost less weight and had less virus in their lungs and other organs than unvaccinated control animals. Vaccinated animals also demonstrated lower mortality. Moreover, the researchers found that neutralising antibody responses were inversely correlated with weight loss and viral loads in respiratory tissues. The Ad26.COV2.S vaccine is currently being evaluated in clinical studies to establish the performance of the vaccine candidate in humans.
"This hamster model of severe COVID-19 disease should prove useful to complement current nonhuman primate models in the evaluation of candidate vaccines and therapeutics," said Barouch, who is also the William Bosworth Castle professor of medicine at Harvard Medical School, a member of the Ragon Institute of MGH, MIT, and Harvard, and the co-leader of the vaccine working group of the Massachusetts Consortium on Pathogen Readiness.
In July 2020, investigators at BIDMC and other institutions initiated a first-in-human Phase 1/2 clinical trial of the Ad26.COV2.S vaccine in healthy volunteers. Dr Kathryn E Stephenson, is the principal investigator for the trial at BIDMC, which is funded by Janssen Vaccines & Prevention, BV, a pharmaceutical research arm of Johnson & Johnson.
Pending clinical trial outcomes, the Ad26.COV2.S vaccine is on track to start a phase 3 efficacy trial in up to 60,000 participants in September 2020.
Co-authors included researchers at Cummings School of Veterinary Medicine at Tufts University; Ragon Institute of MGH, MIT, and Harvard; Oregon Health & Sciences University; and the Massachusetts Institute of Technology.
Abstract 1
Coronavirus disease 2019 (COVID-19) in humans is often a clinically mild illness, but some individuals develop severe pneumonia, respiratory failure and death1,2,3,4. Studies of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infection in hamsters5,6,7 and nonhuman primates8,9,10 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 primates11,12,13. 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.
Authors
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, Dan H Barouch
Abstract 2
A safe and effective vaccine for severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) may be required to end the coronavirus disease 2019 (COVID-19) pandemic1–8. For global deployment and pandemic control, a vaccine that requires only a single immunization would be optimal. Here we show the immunogenicity and protective efficacy of a single dose of adenovirus serotype 26 (Ad26) vector-based vaccines expressing the SARS-CoV-2 spike (S) protein in nonhuman primates. Fifty-two rhesus macaques were immunized with Ad26 vectors encoding S variants or sham control and were challenged with SARS-CoV-2 by the intranasal and intratracheal routes9,10. The optimal Ad26 vaccine induced robust neutralizing antibody responses and provided complete or near-complete protection in bronchoalveolar lavage and nasal swabs following SARS-CoV-2 challenge. Vaccine-elicited neutralizing antibody titres correlated with protective efficacy, suggesting an immune correlate of protection. These data demonstrate robust single-shot vaccine protection against SARS-CoV-2 in nonhuman primates. The optimal Ad26 vector-based vaccine for SARS-CoV-2, termed Ad26.COV2.S, is currently being evaluated in clinical trials.
Authors
Noe B Mercado, Roland Zahn, Frank Wegmann, Carolin Loos, Abishek Chandrashekar, Jingyou Yu, Jinyan Liu, Lauren Peter, Katherine McMahan, Lisa H Tostanoski, Xuan He, David R Martinez, Lucy Rutten, Rinke Bos, Danielle van Manen, Jort Vellinga, Jerome Custers, Johannes P Langedijk, Ted Kwaks, Mark JG Bakkers, David Zuijdgeest, Sietske K. Rosendahl Huber, Caroline Atyeo, Stephanie Fischinger, John S Burke, Jared Feldman, Blake M Hauser, Timothy M Caradonna, Esther A Bondzie, Gabriel Dagotto, Makda S Gebre, Emily Hoffman, Catherine Jacob-Dolan, Marinela Kirilova, Zhenfeng Li, Zijin Lin, Shant H Mahrokhian, Lori F Maxfield, Felix Nampanya, Ramya Nityanandam, Joseph P Nkolola, Shivani Patel, John D Ventura, Kaylee Verrington, Huahua Wan, Laurent Pessaint, Alex Van Ry, Kelvin Blade, Amanda Strasbaugh, Mehtap Cabus, Renita Brown, Anthony Cook, Serge Zouantchangadou, Elyse Teow, Hanne Andersen, Mark G Lewis, Yongfei Cai, Bing Chen, Aaron G Schmidt, R Keith Reeves, Ralph S Baric, Douglas A Lauffenburger, Galit Alter, Paul Stoffels, Mathai Mammen, Johan Van Hoof, Hanneke Schuitemaker, Dan H Barouch
[link url="https://www.bidmc.org/about-bidmc/news/2020/07/covid-19-vaccine-protects-non-human-primates"]Beth Israel Deaconess Medical Centre material[/link]
[link url="https://www.nature.com/articles/s41591-020-1070-6"]Nature Medicine abstract 1[/link]
[link url="https://www.nature.com/articles/s41586-020-2607-z"]Nature abstract[/link]