An HIV lab’s pivot to develop a single-dose Covid-19 vaccine wins STAT Madness ‘Editors’ Pick’

On Jan. 10 last year, Dan Barouch and members of his vaccine research lab were gathered at Boston’s Museum of Science for their annual retreat. The scientists’ ears had pricked up at early word from Wuhan, China, of a strange new virus spreading. That chilled Barouch and his colleagues, who sensed danger in a stealthy pathogen finding a foothold in a world that had never seen the virus before.

That same Friday night, Chinese scientists released the genome they sequenced of the virus, not yet named SARS-CoV-2. Barouch and others left the retreat and went back across town to their vaccine and virology lab at Beth Israel Deaconess Medical Center. For nearly 20 years they had been tackling HIV, and more recently Zika and Ebola, inventing a platform for vaccines that used engineered adenoviruses — like ones that cause the common cold —to ferry pieces of the genetic code of a bad virus into our bodies to induce our immune systems to recognize the invader and protect against it. 

The team downloaded the viral sequence, and over the weekend — alarmed by 41 reported cases in Wuhan — they scrambled to design a vaccine candidate to test.

“We knew the questions to have and we knew how to answer them,” Barouch told STAT last week. “We just had to execute the program in a rapid and flawless way to make it go as quickly as possible.” 

Like labs around the world, Barouch’s pivoted to meet the challenge of Covid-19. The Editors’ Pick award in this year’s STAT Madness contest honors his team for rapidly shifting gears and their work to develop a single-dose, easily shipped and stored vaccine that holds promise as a game-changer for protecting hard-to-reach populations. What Barouch’s lab created became Johnson & Johnson’s Covid-19 vaccine, granted emergency use authorization in the U.S. on Feb. 24. 

STAT’s annual competition to identify the year’s top discoveries in biomedicine started with nearly 130 entries from U.S. research institutions, ranging from developing treatments for “undruggable” targets in cancer to creating microscopic machines from frog cells. We selected 64 for an NCAA basketball tournament-style bracket, based on originality, scientific rigor, and potential impact. After six rounds and more than 1 million votes, readers chose two winners: Fred Hutchinson Cancer Research Center and a collaboration between MIT and Brigham and Women’s Hospital. 

STAT staffers evaluated the 64 entries to come up with the Editors’ Pick. Not surprisingly, in a year dominated by the pandemic, 15 of the 64 involved research related to Covid-19, including characterizing the immune response to the coronavirus; repurposing existing drugs as treatments; understanding why patients’ blood clots; and devising tests using CRISPR as well as sewer water. The Beth Israel Deaconess team’s work on a Covid vaccine stood out because of its innovative approach and immediate impact.

Like the Moderna and Pfizer/BioNTech vaccines, the J&J vaccine is built on a novel design never before approved by regulators. On the usual timescale for vaccine development, all three successes are overnight sensations, but in reality they are constructed on a foundation much longer in the making. 

“Not just our vaccine, but all the vaccines have been a stunning scientific accomplishment that occurred in about a year,” Barouch said. “They were only possible because of decades of scientific advances from many, many groups around the world in virology and immunology, as well as vaccine technology. So although the vaccines, per se, were made in a year and therefore gave rise to the question of whether they were rushed, actually one could argue that the work on the vaccine began 20 years ago.”

That foundation meant that members of Barouch’s team quickly zeroed in on the adenovirus called Ad26, well known to them from their work with HIV, for which a Phase 3 clinical trial is now testing an Ad26-based vaccine. But another, more recent disease provided a better model for Covid-19, Barouch said.

The Zika epidemic emerged in 2015, causing grievous birth defects in children whose mothers contracted the illness while they were pregnant. While the challenges for making a HIV vaccine are unique to HIV, the Zika virus is more typical. It showed clear evidence of generating natural immunity in infected people, making it more straightforward to develop a vaccine. The Zika vaccine they developed was a single-shot vaccine, and that’s what led them to do the same for Covid, Barouch said. Working with J&J, they were never able to do an efficacy trial for Zika because after 2017, there wasn’t enough disease around to test protection. 

Another partnership with J&J on an Ad26-based vaccine against Ebola took advantage of the large pharmaceutical company’s ability to formulate and manufacture a vaccine in a single dose that didn’t need to be kept frozen. (In contrast, the Pfizer/BioNTech and Moderna vaccines must be kept at ultracold temperatures and require two doses.)

Two weeks after that January 2020 retreat, the team reached an agreement with J&J to develop a Covid-19 vaccine. Soon after, much of the world was in lockdown. Only scientists working directly on Covid were allowed in the lab. “It’s surreal to be working on a vaccine while the virus is literally floating around the world, in our country, and in my very own city in Boston,” Barouch recalled.

Lab members dropped other projects to work on the Covid vaccine. By summer, with the lockdown over and the vaccine headed for clinical trials after success in animals, some people in Barouch’s lab returned to other projects. But the work continues to see if next-generation Covid vaccines will be necessary.

Viral variants, of course, are the concern, but less so with the J&J vaccine because it was tested later in the pandemic and in different countries than the mRNA-based shots. In South Africa, for example, the J&J vaccine did well against the B.1.351 variant that first circulated there. Barouch does allow that new formulations or boosters may be needed, but he has set his sights higher.

“I do think that in the future, it would be good to have vaccines that are more class-based on viruses rather than vaccines that are strictly for one pathogen,” he said. “We have to be prepared for any eventuality.” 

This year’s lab retreat was a virtual affair, held on Jan. 15 before results from the J&J vaccine clinical trial were known. Once the Moderna and Pfizer/BioNTech vaccines were authorized, Barouch urged everyone he knew to take whichever one became available to them.

He waited for J&J’s.

“It was a very personal and emotional experience to get vaccinated with the vaccine that I helped create,” he said.