Investigational COVID-19 vaccine candidate prevents se-vere clinical disease in animals

September 03, 2020

Boston, Mass. - 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 Center (BIDMC) immunologist Dan H. Barouch, MD, PhD, and colleagues showed in recently published previous work that a candidate COVID-19 vaccine raised neutralizing antibodies that robustly protected non-human primates (NHPs) against SARS-CoV-2, the virus that causes COVID-19. Now, in new research published to-day in Nature Medicine, Barouch and colleagues demonstrated that the optimal vaccine elicited robust im-mune 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 ma-caques, and this vaccine is currently being evaluated in humans," said Barouch, who is Director of BIDMC's Center 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 neutralizing antibodies.

In the current study, the researchers immunized 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 ani-mals 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 neutralizing 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 pri-mate 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. Kathryn E. Stephenson, MD, MPH, is the principal investiga-tor for the trial at BIDMC, which is funded by Janssen Vaccines & Prevention, B.V., a pharmaceutical re-search 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 Lisa H. Tostanoski, Katherine McMahan, Noe D. Mercado, Jingyou Yu, Cesar Piedra-Mora, Esther A. Bondzie, Gabriel Dagotto, Make S. Gebre, Catherine Jacob-Dolan, Fijian Lin, Shant H. Mahrokian, Felix Nampanya, and Ramya Nityanandam of BIDMC; Frank Wegman, Jerome Custers, Hanneke Schiutemaker, and Roland Zahn of Janssen Vaccines & Prevention BV; Amanda J. Martinot, Linda M. Wrijil, and Sarah Ducat of Cummings School of Veterinary Medicine at Tufts University; Carolin Loos, Caroline Atyeo, Stephanie Fischinger, John S. Burke, Jared Feldman, Blake M. Hauser, Timothy M. Caradonna, Galit Alter, and Aaron G. Schmidt of Ragon Institute of MGH, MIT, and Harvard; Chi N. Chan, Stephen Bondoc, Carly E. Starke, Michael Nekorchuck, Kathleen Busman-Sahay, Jacob D. Estes of Oregon Health & Sciences University; Laurent Pessaint, Maciel Porto, Vanessa Ali, Dalia Benetiene, Komlan Tevi, Hanne Andersen, and Mark G. Lewis of Bioqual; and Douglas A. Lauffenburger of Massachusetts Institute of Technology.

Barouch, Wegman, Custers, Schuitemaker, and Zahn are co-inventors on related vaccine patents. Wegman, Custers, Schuitemaker, and Zahn are employees of Janssen Vaccines & Prevention BV and hold stock in Johnson & Johnson.

This project was funded in part by the Bill & Melinda Gates Foundation (INV- 226 006131); Janssen Vac-cines & Prevention BV; Ragon Institute of MGH, MIT, and Harvard; Mark and Lisa Schwartz Foundation; Massachusetts Consortium on Pathogen Readiness (MassCPR); the National Institutes of Health (OD024917, AI129797, AI124377, AI128751, AI126603 to D.H.B.; AI007387 to L.H.T.; AI146779 to A.G.S.; AI135098 to A.J.M.; and OD011092, OD025002 to J.D.E.); the Department of Health and Human Services Biomedical Advanced Research and Development Authority (BARDA) under contract HHS0100201700018C; a Fast Grant, Emergent Ventures, Mercatus Center at George Mason University to A.J.M.

About Beth Israel Deaconess Medical Center

Beth Israel Deaconess Medical Center is a patient care, teaching and research affiliate of Harvard Medical School and consistently ranks as a national leader among independent hospitals in National Institutes of Health funding. BIDMC is the official hospital of the Boston Red Sox. For more information, vis-it

Beth Israel Deaconess Medical Center is a part of Beth Israel Lahey Health, a new health care system that brings together academic medical centers and teaching hospitals, community and specialty hospitals, more than 4,000 physicians and 35,000 employees in a shared mission to expand access to great care and ad-vance the science and practice of medicine through groundbreaking research and education.

Beth Israel Deaconess Medical Center

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