414 days at work, zero days off: Dan Barouch and the race to develop the Johnson & Johnson vaccine

If you guessed the vaccines produced by Moderna and Pfizer, you wouldn’t be wrong. But you wouldn’t be right unless you also included the Johnson & Johnson vaccine.

The comparatively low 66 percent efficacy rate that Johnson & Johnson (Janssen) initially reported was based on a single shot, in international trials. J&J was, after all, designed for an easy “one and done” rollout around the globe. The early Moderna and Pfizer trials were based on two shots, in the United States (or, in the case of Pfizer, mostly in the US). When the J&J vaccine was later tested with two shots in this country — that is, a booster two months after the original jab — the efficacy rate climbed to 94 percent.

If you missed that nuance, it’s understandable. Immunological analysis is a lot harder than second-guessing the wisdom of bringing Jackie Bradley Jr. and his .163 batting average back to Boston.

Dr. Dan Barouch, the Harvard Medical School professor who heads Beth Israel Deaconess’ Center for Virology and Vaccine Research, led the early development of the J&J vaccine. In the race to outsmart a raging virus, the world was fortunate to have the 48-year-old Barouch working relentlessly on its behalf.

During the terrifying early months of the pandemic, it would have seemed absurd to predict that scientists could devise and deploy a successful COVID vaccine within a single year. But Barouch and company did exactly that. So it’s more than a little curious that the popular image of the J&J vaccine, at least in this country, is that of an under-loved third choice.

Not that the rollout of the J&J vaccine wasn’t weighed down with some serious problems — it was. And not that the messenger RNA vaccines produced by Moderna and Pfizer, and given emergency approval in 2020, aren’t remarkably innovative and effective — they are.

But there’s no denying that J&J has had a profound impact, especially around the world. As of October, according to The New York Times, Moderna had shipped only about 1 million doses of its COVID vaccine to the world’s poorest countries, compared with the 25 million doses that J&J had shipped. Because of J&J’s single-shot design and ability to be stored for up to six months at normal refrigeration, for many rural areas, developing countries, and hard-to-reach populations, it’s not just another vaccine option — it’s the only realistic one. In that way, it has enormous potential to help save millions of lives in the most vulnerable parts of the world.

And as Barouch now turns his attention to trying to beat back the newest variant while also learning more about the lasting impact of each of the vaccines, the one he helped create holds the promise of taking on even more importance.

At 6:27 p.m. on January 28 of this year, Barouch and his family were just about to sit down for dinner in their Newton home when an e-mail came through. The subject line read: “Super confidential.” Dr. Mathai Mammen, J&J’s head of research and development, was sending along the Phase 3 clinical results the company would report the next day. “Congratulations,” Mammen wrote, “on a vaccine that will help the world!”

Barouch shared the news with his wife, Dr. Fina Barouch. The ophthalmologist called over their two daughters, who are 14 and 11, and told them, “The vaccine that Daddy’s been working on worked!” Then she opened the fridge and dug out a bottle of champagne.

In some ways, Barouch had been training his whole life to meet this moment. He grew up in an academic family in Potsdam, New York — his father was a professor of math and computer science, his mother a PhD in biochemistry. He enrolled at Harvard at age 16 and then deferred his acceptance to Harvard Medical School so he could study at Oxford. By the time he returned to Boston, he had earned his PhD and developed a deep interest in immunology.

He’d been working for more than a decade to develop an HIV vaccine when, in 2016, he temporarily pivoted his team to meet the new threat of the Zika virus. When coronavirus arrived in January 2020, he says, “We basically applied the vaccine platform that we had developed for HIV and perfected for Zika to a new global threat.”

How did he celebrate when the Food and Drug Administration approved emergency use of the J&J vaccine on February 27? He took his first day off in 414 days — and he slept.

Then, in early April, federal officials paused Johnson & Johnson’s rollout. Six women who received the J&J shot had developed unusual blood clots, and one of them died. Barouch was saddened for them — and worried for the future. “I had a lot of concern as to whether this was truly a very rare complication or whether it actually might just be the tip of the iceberg,” Barouch tells me. If it was the latter, he knew, “The vaccine would have to be pulled.”

No iceberg emerged. Ten days later, the feds lifted their pause, adding a warning about the rare side effect to the vaccine’s label. That same month, the FDA halted manufacturing of the J&J vaccine at a Baltimore plant because of contamination concerns.

These were serious setbacks, but mild when put into historical perspective. During the rollout of Dr. Jonas Salk’s polio vaccine in 1955, a California manufacturing plant accidentally produced vaccines containing the live virus. That led to tens of thousands of cases of polio, the paralysis of 200 children, and the death of 10. Yet in a response that would seem unimaginable today, parents continued to get their children vaccinated at extremely high rates. And that trust in science allowed the nation to conquer the scourge of polio.

The Barouch lab has also been working to understand the kind of protection each of the vaccines offers over time. As codirector of the lab’s Clinical Trials Unit, Dr. Ai-Ris Collier works closely with Barouch. That has led her to formulate one hypothesis about him: “I don’t think he sleeps at all.”

Collier is trying to tease out the so-called durability of the vaccines. What levels of protective immune response remain in vaccinated people long after they’ve had their last shot? While there’s a lot that researchers still don’t know about durability, Collier says the early results hold particular promise for J&J. Compared with the two-shot mRNA varieties, J&J’s single shot produces a smaller immediate immune response in people, but it seems to hold steady for longer. “After eight months,” she says, the responses “look pretty similar.” That pattern could hold important clues in the hunt for a long-term approach to combating COVID.

Of course, there’s a chance that the wily new Omicron variant will end up extinguishing that promise. But in this crisis of confidence, it’s worth remembering when the outbreak of the Delta variant in Provincetown this summer shook us. How could more than 1,000 people get COVID in a couple of weeks when three-quarters of them had been vaccinated? It seemed like a case study in vaccine failure.

The state asked Barouch and his team to study the P-town outbreak. What they found, described in a paper published this fall, was reassuring. “If you’re vaccinated and you get a breakthrough infection, then you will likely have only mild illness, and you’ll have a massive increase in your immune responses,” Barouch says. Provincetown wasn’t a case study in vaccine failure, after all; it was the latest vaccine success story in an increasingly long line of them.

Working on vaccines during a pandemic is an exhausting, Sisyphean challenge. Yet no matter what setbacks and uncertainty 2022 brings us, we can count on this: A sleepless Barouch will be in his lab, helping to push that rock back up the hill.

Neil Swidey is editor at large of the Globe Magazine. Send comments to magazine@globe.com.

As COVID-19 first emerged, scientists raced to develop novel vaccines in record time — and are rightly celebrated for their breakthroughs. But the work has also required legions of local, less-heralded manufacturing workers to bring vaccines, and now boosters, from the lab to your arm.

Starting in the spring of 2020 at Pfizer’s facility in Andover, some 400 scientists, technicians, and engineers clocked in seven days a week, working overtime and on holidays. They were ramping up production of mRNA, the key component of the vaccine, which is frozen and delivered to other facilities to be made into finished doses. The effort included a hiring spree of more than 350 people in process development, quality control, and manufacturing, and their work is getting results. Pfizer has already produced 3 billion vials, double the company’s initial projections, and is on track to deliver 4 billion in 2022.

At Moderna’s manufacturing plant in Norwood, one of a number of facilities where its vaccine is made, a similar race-turned-marathon was being run. Just 42 days after COVID’s genetic code was published, the company shipped a few hundred vials of its new vaccine to the National Institute of Allergy and Infectious Diseases in Bethesda, Maryland. But it would take hundreds of employees working overtime to ramp up its production. Today, the Norwood plant is still operating at full speed, even as it’s under construction. Moderna announced in May that it would more than double its 300,000-square-foot space to help meet its worldwide goal of producing 3 billion doses next year.

—Jessie Scanlon

Neil Swidey is the Globe Magazine editor at large. He can be reached at neil.swidey@globe.com.