Dan Barouch, MD, PhD (Center for Virology and Vaccine Research, BIDMC) discusses how the decades-long investment in HIV research has helped to further boost the research for a COVID-19 vaccine.

Washington Post – July 14, 2020

A caretaker cuddles a baby infected with HIV in 1988 at the nonprofit Grandma’s House in Washington. (Frank Johnston/The Washington Post)

Decades of research on an HIV vaccine boosts the bid for one against coronavirus

In 1984, scientists discovered the virus at the root of an alarming epidemic that was sickening otherwise healthy young men with aggressive cancers and rare, life-threatening pneumonias.

The discovery of HIV was a long-awaited moment, and Health and Human Services Secretary Margaret Heckler vowed that the scourge of AIDS would soon end. A vaccine would be ready for testing within two years, she proclaimed.

“Yet another terrible disease is about to yield to patience, persistence and outright genius,” Heckler said.

Thirty-six years later, there still is no HIV vaccine. But instead of being a cautionary tale of scientific hubris, that unsuccessful effort is leading to even greater confidence in the search for a coronavirus vaccine, from some of the same researchers who have spent their careers seeking a cure for AIDS.

Those decades of research on HIV have taught scientists an enormous amount about the immune system, honed vaccine technologies now being repurposed against the coronavirus and created a worldwide infrastructure of clinical trial networks that can be pivoted from HIV to the pathogen that causes the disease covid-19.

Laboratories, testing sites and recruitment networks that were rushed into action against the coronavirus exist because of the enormous amount of money spent on HIV. Equipment and expertise are in place. Infection control has been upgraded. Regulators are engaged.

“The investment in HIV research has made the response to covid-19 possible,” said Dan H. Barouch, director of the Center for Virology and Vaccine Research at Beth Israel Deaconess Medical Center in Boston, whose work on an HIV vaccine has led to one of the leading candidates for a coronavirus vaccine.

“Bring it on, we’re ready and waiting for the covid vaccine trials,” said Linda-Gail Bekker, deputy director of the Desmond Tutu HIV Center at the Institute of Infectious Disease and Molecular Medicine at the University of Cape Town in South Africa.

HIV is a devilishly complicated virus, deft at outwitting vaccine efforts, but there are real reasons to hope that the coronavirus will be a less resilient foe. Only by piggybacking on the HIV vaccine effort, though, can coronavirus research move so fast.

“It’s really been a dramatic and rapid pivot for the people who are leaders in the HIV vaccine and prevention community,” said Nina Russell, deputy director for tuberculosis and HIV programs at the Bill & Melinda Gates Foundation.

Between 2000 and 2018, about $14.5 billion was spent on research toward an HIV vaccine, according to the Resource Tracking for HIV Prevention Research and Development Working Group, a project of the advocacy organization AVAC. Forty-six vaccines have survived to the preclinical or clinical stages of evaluation, and 100 were abandoned earlier in the process, the group’s data shows.

In contrast, there are 160 vaccines under development for the novel coronavirus, a pathogen unknown to science a little more than six months ago, according to a list kept by the World Health Organization. Twenty-one of them are being evaluated in clinical settings. Billions of dollars have been committed by governments and private companies.

Now the two efforts are dovetailing.

“HIV has a lot of researchers in immunology and virology who set up labs, who have [vaccine] platforms, and they are looking to quickly repurpose to see if they can find a coronavirus vaccine,” said Meg Doherty, director of the WHO’s department of global HIV, hepatitis and STI programs.

A model of the coronavirus sits next to a nameplate for Francis Collins, director of the National Institutes of Health, before his testimony on Capitol Hill this month. (Saul Loeb/Pool)

Two viruses, key differences

Science is gambling that one or more of those efforts will yield and deploy a coronavirus vaccine within 12 to 18 months. Researchers are heartened by the key differences between the viruses. HIV integrates itself into the body’s cells, which means a vaccine has to start working immediately to rout it. People’s immune systems are not able to naturally defeat HIV, making a vaccine even more difficult to create. And it mutates much more quickly than the novel coronavirus, officially named SARS-CoV-2.

“It certainly won’t be easy, but what gives me hope is the natural history of this infection,” said Francis Collins, director of the National Institutes of Health. The large number of people who experience mild covid-19 symptoms or none at all is a good sign that the immune system can defeat the virus.

“That’s different than HIV,” Collins said. “This is the kind of candidate where the vaccine should work. You know the immune system, given the appropriate priming, is able to eliminate the virus.”

Years of research on vaccines have helped scientists perfect technologies and methods that can be repurposed for the coronavirus, from RNA and DNA vaccines to those that use harmless viruses to deliver genes from the targeted virus to cells.

Barouch, for example, has spent 15 years focused on HIV vaccine research. He developed a technology based on a harmless cold virus that could ferry specific genes into cells. Those genes code for a distinctive part of the AIDS virus to create an immune response.

The HIV vaccine based on that work, under development with the pharmaceutical giant Johnson & Johnson, was being tested in clinical trials on a Friday in early January when Barouch was holding his annual lab retreat at Boston’s Museum of Science. A main topic of discussion was a new pneumonia in Wuhan, China, with 41 known cases and one death at the time.

The numbers seem small today, with more than 13 million cases confirmed around the globe, but Barouch and his laboratory found the news alarming even then. They decided they should do something.

That evening, the genome sequence of the virus was shared online by researchers in China, and Barouch’s lab began studying it. It didn’t take long to connect with Johnson & Johnson to work on a vaccine expected to begin human testing this month.

They repurposed the vaccine platform originally developed for HIV and Ebola by inserting genetic material that codes for the coronavirus’s distinctive spike protein. That should, in theory, trigger the immune system to develop coronavirus-fighting antibodies that protect people from infection. If it weren’t for HIV, Barouch said, his laboratory and its industry partner would not have been able to move so rapidly.

‘They’re there and ready to go’

Over the years, the United States has built a large network to conduct the logistically complex clinical trials necessary to test HIV vaccines and preventive drugs. Larry Corey, a virologist and past president of the Fred Hutchinson Cancer Research Center in Seattle who is co-leading the Covid-19 Prevention Trials Network, said almost every aspect of running 30,000-person clinical trials for vaccines is built on the foundation of HIV.

Those range from data collection and biostatistics expertise to analyze large trials to community relationships and experience in recruiting vulnerable people into complicated medical experiments.

The NIH unveiled its COVID-19Prevention Network on Wednesday. It is an amalgamation of several large clinical trial networks, two of them directly taken from HIV.

Leaders acknowledge that the challenges and scale are different: Not everyone is at risk of HIV, while the world population is vulnerable to the coronavirus.

Corey said that while a network might have spent years preparing to launch the trials now contemplated, it has to be done in only weeks. However, the more mundane but essential aspects of clinical trials that ensure the results are unassailable are all in place: freezers that have been audited to show they never fail, personnel experienced at recruiting participants, operations managers accustomed to running years-long experiments.

“The NIH has invested a tremendous amount of money over the years in developing an international network capable of doing these types of trials, which requires a tremendous amount of infrastructure,” said Richard Novak, chief of infectious diseases at the University of Illinois at Chicago’s College of Medicine. “Fortunately they’re there and ready to go when something like this comes along. Otherwise, it would take years to develop.”

A critical lesson from HIV, the University of Cape Town’s Bekker said, is taking numerous approaches to a vaccine at the same time. HIV vaccine experiments often tended to be staged one after another, with the entire community waiting for the results of the best candidates. In contrast, numerous coronavirus trials are occurring simultaneously.

“If you want to do this quickly and you want to be sure you have a winner, then put a number of horses in the race that do a number of different things,” she said. And with the global population threatened, several safe, effective vaccines may be needed.

The world “may need more than one winner,” Bekker said.

Leaders of the effort say years of experience engaging and building trust with minority, vulnerable and marginalized communities for HIV trials will help. But the coronavirus adds new complexities because of the speed and the scale of the trials. Older people in minority communities, for example, haven’t traditionally been the focus of HIV prevention trials, but they are a critical population to protect from the coronavirus.

“We’re going to need to be humble about the fact that we haven’t worked with some of these populations before,” said Nelson Michael, director of the Center for Infectious Diseases Research at the Walter Reed Army Institute of Research.