JOIN USInside Johnson & Johnson's hunt for Covid-19 vaccine
Each workday morning in March, Noe Mercado drove through the desolate streets of Boston to a tall glass building on Blackfan Circle, in the heart of the city’s biotech hub. Most residents had gone into hiding from the coronavirus, but Mercado had an essential job: searching for a vaccine against this new, devastating pathogen.
Parking in the underground lot, he put on a mask and rode the empty elevator to the tenth floor, joining a skeleton crew at the Center for Virology and Vaccine Research at Beth Israel Deaconess Medical Center. Day after day, Mercado sat at his lab bench, searching for signs of the virus in nasal swabs taken from dozens of monkeys.
The animals had been injected with experimental vaccines Mercado had helped create. The monkeys then had been exposed to the coronavirus, and now Mercado was finding out whether any vaccine had protected them. One morning, after he loaded all the data into a software program, a single telling graph set his heart beating: Some of the vaccines, it appeared, had worked.
Mercado hurried around the lab to share the news. Given the times, there were no hugs, no high-fives. And he did not bask in glory for long. Making a vaccine demands patience, attention to detail — and a tolerance for bitter failure.
“Yeah, I’m excited, but I’m also thinking about the next step,” Mercado later recalled. “What if it doesn’t pan out?”
The coronavirus has now infected about 13.8 million people worldwide and killed at least 590,000. Millions more may die. The only hope for a long-term protection, literally the only shot at a return to normal life, is an effective vaccine. In January, researchers at the vaccine center dropped everything they were doing to find one. The man heading up the effort is Mercado’s boss, Dr. Dan Barouch, the director of the center and one of the world’s leading vaccine-makers.
Now they are about to take a major step forward. Janssen Pharmaceutica, a division of Johnson & Johnson, has been collaborating with the Beth Israel team to craft a coronavirus vaccine based on a design pioneered by Dr. Barouch and his colleagues ten years ago.
Next week, clinical trials of the vaccine will begin in Belgium. Dr. Barouch’s team will soon start up a trial in Boston. The past six months have been a blur of long weeks and late nights, of strict safety measures and scarce lab supplies. “Everything has been orders of magnitude more challenging than in the pre-pandemic era,” Dr. Barouch said.
Researchers around the world have been making vaccines of their own, some with dead viruses, others with protein fragments and strings of DNA. As of July, there are over 135 vaccines in preclinical tests, and another 30 in clinical trials on people. Never have so many vaccines moved so quickly into trials for one disease.
Since January, Dr. Barouch’s team in Boston has run experiments in cells and monkeys, while Janssen’s researchers in the Netherlands have raced to find a recipe for producing the new vaccine in huge quantities. Already they have started producing a batch for the clinical trials.
If the vaccine proves safe in initial tests, a trial for efficacy will launch in September. If that experiment is successful, Johnson & Johnson will manufacture hundreds of millions of doses for emergency use in January. Over the course of next year, the company plans to produce up to a billion doses.
While Johnson & Johnson is one of the world’s biggest companies, with a market capitalization over $370 billion, it’s a fairly small player in the vaccine market. On July 1, its Ebola vaccine received approval from the European Commission. The company’s vaccines for other diseases are still in clinical trials.
Even so, the United States government has given $456 million to Johnson & Johnson, funding from the Trump administration’s Operation Warp Speed; the company has invested another $500 million in the coronavirus vaccine project.
Dr. Barouch and his colleagues are now finishing up tests of the final formulation in monkeys. In the next few months, they will begin to see how people respond to the injection.
It is a monumental task to develop a vaccine so quickly against a pathogen that no one had heard of before this year. But, Dr. Barouch said, “I’m even more optimistic now than I was several months ago.” As January wore on, Dr. Barouch realized that Covid-19 was going to be far graver threat than SARS.
“We would not be able to stop this virus by traditional public health measures,” he said. “It was absolutely clear that we needed a vaccine.”
He emailed to Johan Van Hoof, the head of vaccines at Janssen. “I am writing today because the coronavirus outbreak in China is looking bad,” Dr. Barouch wrote. “Are you interested in making a rapid Ad based vaccine like we did for Zika in 2016-2017?”
Two minutes later, Dr. Van Hoof replied: “Would a call work now?” And four days after the call, they signed an agreement to collaborate. The Center for Virology and Vaccine Research has a staff of dozens of researchers, ranging from medical doctors and senior scientists to postdoctoral researchers, grad students and assistants just out of college. Dr. Barouch’s team turned away from projects on H.I.V. and other diseases, and divided up the work to make a coronavirus vaccine.
Mercado and his colleagues fashioned copies of the coronavirus gene that directs production of its spike protein. They came up with ten variations to see which would produce the best immune response.
Meanwhile, Katherine McMahan, a research assistant at the center, worked on the team building a test for spike antibodies in the animals that would receive the vaccine. Creating it took up most of her waking life. On some days, she didn’t get around to eating lunch till nighttime. In late February, researchers injected the spike genes into mice and then sent Ms. McMahan blood from the animals. Ms. McMahan’s test confirmed that they were making coronavirus antibodies.
Ms. McMahan was near tears: “It began to feel like a war that we could win.”
Outside the lab, though, there was no sense that a war was coming. She urged family and friends to stock up on food and other supplies, without much luck. The nasal swabs that Mercado examined revealed that some versions of the vaccines only partially protected the monkey, but others worked much better. As the investigators reported in the journal Science, they couldn’t detect the virus at all in eight of the 25 monkeys who got experimental vaccines.
The results gave Dr. Barouch hope that one of his team’s vaccines — or one of those developed by another group — might work. “It’s the real deal,” he said. More monkeys were injected with the Ad26 virus, now equipped to produce the spike gene. Dr. Barouch predicts that this vaccine will induce higher levels of antibodies than the prototypes did.
The experiment will also provide crucial clues about how the immune system responds to the Ad26 vaccine. Some vaccines confer protection mostly by triggering the body to make antibodies that attack a virus. But others can stir virus-hunting immune cells to join the attack.
The results of the latest round of experiments will be published within a few weeks. For all the progress made by Dr. Barouch’s team, the Ad26 vaccine has its skeptics. John Moore, a virologist at Weill Cornell Medical College, said other types of vaccines tested in animals have produced higher levels of antibodies. These vaccines, made of viral proteins, would be his choice for a weapon against the coronavirus.
One drawback of viral-protein vaccines is that they take more time to produce in huge quantities. Other vaccines, like Johnson & Johnson’s Ad26, will come more quickly, and Dr. Moore acknowledged that they may work well enough to provide protection.
If so, there may not be a need for a better but slower vaccine. “If Plan A works, then you don’t need a Plan B,” Dr. Moore said. Amid a pandemic, critics say Johnson & Johnson should not be allowed to set the terms. “If we get a vaccine, it should be free and available to everybody,” said the Rev. Dr. William J. Barber II, the president of the North Carolina N.A.A.C.P. and a critic of Johnson & Johnson’s drug pricing.
“How do you get these big, massive awards to produce a vaccine without any rider on the money saying it must be used in a way that it’s affordable to everybody?” he asked.
For now, no one knows if the vaccine will actually work. Dr. Barouch and his colleagues are getting ready to inject the Ad26 vaccine into hundreds of volunteers in Boston in late July. Researchers will not only observe whether the vaccine is safe but also look at the antibodies it prompts the volunteers to make. If those trials produce promising results, Johnson & Johnson will run a much larger one in the fall to see if the vaccine is effective.
At the same time, Dr. Barouch and his colleagues are planning a third round of experiments on monkeys. They want to inject the animals with antibodies against the coronavirus and then infect them. By giving different monkeys varying doses, the investigators hope to figure out what level of antibodies in the human body is required to prevent Covid-19.