The research Jeffrey Cirillo is leading at Texas A&M University won't produce a vaccine to prevent people from contracting COVID-19, but while other labs pursue a full-blown preventive, his work could offer a critical bridge to help keep more infected people alive.
Working with a consortium of research institutions, Cirillo, a professor of microbial pathogenesis and immunology at the A&M Health Science Center, and his team are launching tests on health care workers to see if a decades-old tuberculosis vaccine might also help drive down the number of people who are hospitalized or die from the new coronavirus. The urgency of that task now fills his days.
“I’m very acutely aware that the longer it takes us to get this vaccine out … the more health care workers get exposed, get infected and get ill and the more people die,” Cirillo said. “We just don't have time. Every time we get a delay of a day or two, it matters.”
Scientists have known for decades that the tuberculosis vaccine, called bacille Calmette-Guerin, or BCG, improves immunity against some viruses. It’s been used more than a billion times around the world in countries where tuberculosis is common, said Andrew DiNardo, an infectious disease specialist at Baylor College of Medicine, who is leading the trial’s efforts there.
The vaccine contains active tuberculosis cultures, and the U.S. Centers for Disease Control and Prevention generally recommends against using it in part because of “the low risk of infection” with the bacteria that causes tuberculosis in humans. It is, however, used in the United States for treating bladder cancer, effectively rekindling the immune system to fight off cancer cells.
Researchers hope it may have a similar effect in coronavirus patients, boosting their immune response to increase their chances of fighting off the disease.
In March, DiNardo and a group of other researchers studying tuberculosis asked: Why aren’t we using BCG against COVID-19?
“We knew the literature on this, and we emailed the world expert on it,” said DiNardo, referring to a similar study being conducted in the Netherlands by immunologist Mihai Netea. “And he said, ‘Yeah, we're already trying, please help us.’”
Cirillo and DiNardo are working with researchers from Texas A&M, the Baylor College of Medicine, the University of Texas MD Anderson Cancer Center, Harvard’s School of Public Health and Cedars Sinai Medical Center.
The team is recruiting 1,800 health care workers – people on the front lines fighting the virus – to vaccinate. But the vaccine must be tested on people who have not yet been exposed.
For the researchers, that means the pressure is on. Playing soccer has always melted away Cirillo’s stress after a long day at work. Usually he kicks the ball around for a couple of hours. These days, though, he’s lucky to squeeze in 15 minutes.
“I like working on things that are slow and boring,” DiNardo said. “I've never had to work on something that's this pressing, and that there's such a dire need for.”
While working remotely to get the trial off the ground, tracking down needles and nailing down safety protocols for vaccinating hundreds of volunteers, Cirillo said he must also closely monitor the stress levels of his team. He’s not used to checking in with colleagues over computer screens and group texts.
“We're all under the stress of both having this pandemic going on, as well as having the pressure of getting work done,” Cirillo said. “There's a lot of pieces to this puzzle, and we have to put all the pieces together as quickly as we possibly can.”
The researchers were able to skip the first three phases of clinical trials usually required by the U.S. Food and Drug Administration before human testing because the vaccine has already passed those phases and been proven safe for other uses, Cirillo said.
Finding the money needed to get the trials underway posed an early challenge. Cirillo said he spent hours calling potential investors and filling out grant applications — with little success.
“I submitted, just during the first week, five to 10 applications to various agencies per day, and we were talking to different groups, philanthropies, people, venture capitalists, that were interested in doing something but didn't know what to do,” Cirillo said. “But when you start talking about $2.5 million, which was the basic cost that would really get us rolling on this, nobody had that amount of money available.”
When school officials approached Texas A&M University System Chancellor John Sharp about their fundraising challenges, he agreed to foot the bill from his Chancellor’s Research Initiative.
“I took the fundraising out of it and allowed him [Cirillo] to get started,” Sharp said. “You hear people talk about vaccines taking years, but this could be a treatment way, way sooner than that.”
With funding in hand, the team is focusing on recruiting and vaccinating health care workers. The A&M internal review board that screens human studies has approved vaccinating 700 volunteers starting this week. Baylor College of Medicine and UT's MD Anderson together will have approval for 350 subjects, Harvard will have approval for 350 subjects and Cedars Sinai in Los Angeles has approval for 400 subjects, Cirillo said. The researchers hope to expand the trial after six months to first responders, food service workers and older people and eventually to the general public.
Researchers will monitor the volunteers’ health over the next six months, Cirillo said. If the vaccine is working, he said they will see a difference in the overall health of those vaccinated compared with a group that will receive a placebo treatment.
Given the nature of their jobs, it is likely that many of the health care workers who volunteer will be exposed to the virus. Cirillo said the team expects a large number of cases over the next few weeks.
“Since these are health care workers, we expect that they will very rapidly make us aware of any changes in their health, in addition to the weekly health checks,” Cirillo said. “If they have symptoms of COVID-19, we follow them continuously until the infection resolves and will continue the same follow-up with health checks weekly and blood work monthly until the end of the trial.”
Researchers will need to find ways to produce large amounts of the vaccine, Cirillo said. That may require using producers outside of the United States, which takes more time.
Recruitment of health care workers is underway in College Station and Houston, with Los Angeles, Boston and potentially other Texas cities like Round Rock and Dallas to follow. For the initial testing, UT’s MD Anderson Cancer Center is supplying BCG vaccines that it already had on hand.
“There's been a tremendous outpouring of people who have recognized that there's something right now that we already know how it works,” DiNardo said. “We're not trying to develop a vaccine; the vaccine was developed in the 1930s. That's the advantage. Now we’re just rushing against the clock.”
Disclosure: The Texas A&M University System, Baylor University and the University of Texas MD Anderson Cancer Center have been financial supporters of The Texas Tribune, a nonprofit, nonpartisan news organization that is funded in part by donations from members, foundations and corporate sponsors. Financial supporters play no role in the Tribune's journalism. Find a complete list of them here.