Most people with COVID-19 have relatively mild disease, but a subset of people develop severe pneumonia and respiratory failure, sometimes leading to death.
In new research published Sept. 3 in Nature Medicine, Beth Israel Deaconess Medical Center immunologist Dan H. Barouch and co-investigators from Cummings School of Veterinary Medicine demonstrated that a candidate COVID-19 vaccine not only elicited a robust immune response, but also prevented severe disease in hamsters, including weight loss, pneumonia, and death.
Barouch and his BIDMC colleagues showed in work published in late July that a candidate COVID-19 vaccine raised neutralizing antibodies and robustly protected non-human primates against SARS-CoV-2, the virus that causes COVID-19.
The vaccine—developed through a collaboration between BIDMC and Johnson & Johnson—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.
“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, director of BIDMC’s Center for Virology and Vaccine Research.
However, as researchers race to find ways to develop a vaccine and therapies for COVID-19, one concern is that relying solely on the use of monkeys to learn about the efficacy of new therapies is far from ideal. While monkeys have an immune response most similar to humans and are critical for evaluating safety of novel therapeutics, they develop only very mild disease after exposure to SARS-CoV-2.
Hamsters, on the other hand, develop more severe disease, “with pathology that mirrors what has been seen in cases of terminal COVID-19 in people,” said Cummings School assistant professor Amanda Martinot, a veterinary pathologist and one of the first authors on the Nature Medicine study.
Together with Barouch, Martinot is using a $250,000 award from Fast Grants to evaluate how animal studies can reveal what the virus is doing in the body over the first seven days of infection with COVID-19.
“This hamster model can help fast-track the development of not just a vaccine, but also interventional therapeutics,” Martinot said. “If you want to test an anti-inflammatory or antiviral drug, the hamster model looks like it will be very useful in a preclinical setting to try to get a read on whether a novel drug is going to improve outcomes.”
For the vaccine study published in Nature Medicine, the researchers immunized 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 substantially less weight and had markedly less virus in their lungs and other organs than unvaccinated control animals. Vaccinated animals also demonstrated lower mortality.
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. 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.
Genevieve Rajewski can be reached at genevieve.rajewski@tufts.edu.
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September 04, 2020 at 11:08PM
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