About a year ago, Dr. Jesse Clark was taking care of people hospitalized with COVID when he met a man he'll never forget.
"I thought he was sleeping," says Clark, who's an infectious disease specialist at the University of California, Los Angeles. The man was lying still in the bed. "But when I got around to the other side of the bed, he looked up at me and said, 'My mother just died of COVID. My cousin brought this into the family. She said she was wearing a mask, but she didn't. She got COVID. Now she's dead, too. She has two kids. What's going to happen to them?' "
Then the man says, "Am I going to die of COVID?"
The man was doing well enough to fight off SARS-CoV-2, Clark says. And eventually he recovered. But that moment lingered in Clark's memory because it reminded him of another incredibly sad – and scary – moment in his life.
It happened when he was a young man during the early stages of the HIV pandemic.
"I am a gay man who grew up in the '80s and '90s, long before we had an effective treatment for HIV. And friends, colleagues, people were dropping dead left and right. And there was nothing you could do about it," Clark says, with a lump in his throat. "And the question was always, 'Am I next?' "
At that time, many people in the LGBTQ community had a constant fear of losing their life, Clark says. "You're trying to help take care of people around you, but you're also wondering, is this going to happen to me?"
But many people outside that community didn't understand the fear prompted by HIV, he says – at least not until early 2020 when COVID hit. "COVID brought that feeling home to a lot of people in a way that HIV had not."
That shift in perspective – or that new understanding – has reignited the fight against HIV, which still kills about 700,000 people each year. "It has spurred people to try to end the HIV epidemic again," Clark says.
While SARS-CoV-2 has a handful of variants, HIV has hundreds of thousands
During the COVID pandemic scientists around the world made history. They developed and launched a new vaccine in record-breaking time. Researchers at the Commonwealth Fund estimate the SARS-CoV-2 vaccines have averted about 2 million deaths and prevented more than 17 million hospitalizations in the U.S. alone.
And there's been a spillover effect: "The pandemic probably accelerated the HIV vaccine field 5 or 10 years within the span of a year," Clark says.
The technology that made that breakthrough possible, the mRNA technology, is giving a much needed boost to the development of an HIV vaccine.
And boy, does the field need that boost..
For nearly 40 years, scientists have been trying to develop an HIV vaccine. Since 2000, the U.S. government, together with philanthropic institutions and pharmaceutical companies, have spent more $15 billion on the endeavor, the National Bureau of Economic Research estimates. And scientists have made little progress.
"Until this point, we've failed, and I hate to say this, but we failed dismally," says Derseee Archary, who's an immunologist at the AIDS research center CAPRISA in Durban, South Africa.
Developing an HIV vaccine has been incredibly challenging for one big reason. Coincidentally, it's the same reason SARS-CoV-2 keeps coming back. That's variants.
Compared to SARS-CoV-2, HIV has many more variants than SARS-Cov-2. We're talking about many, many ... many more.
SARS-CoV-2 has a few variants that keep emerging, but with HIV, there are thousands of variants in each person infected with HIV," says immunologist William Schief at the Scripps Research Institute.
Given that about 38 million people are infected with HIV, there are literally millions of HIV variants on Earth. "All those variants aren't being transmitted [between people], but many are," Schief says. "Hundreds of thousands probably are being transmitted."
COVID pandemic serendipitously gives researchers a new shot at an HIV vaccine
To prevent an HIV infection, a vaccine has to protect against all of those variants – as many as 100,000.
On the surface, that sounds nearly impossible. Nevertheless, Schief and his colleagues have been working to develop such a vaccine for the past decade. It's arguably the most sophisticated vaccine ever attempted.
The vaccine's goal is to teach the immune system to recognize and stop thousands of HIV variants. And it does that by slowly training the immune system, over the course of a series of shots, to create broadly neutralizing antibodies – or antibodies that can take down the HIV virus even when it starts to mutate and evolve inside the body.
In several studies, Schief and his colleagues, along with another research team at the National Institutes of Health, have shown that the experimental vaccine can trigger the production of broadly neutralizing antibodies in mice. It took 7 to 9 shots to create these antibodies, Schief says. But he hopes the vaccine will work more efficiently in people.
"In humans, we don't think it's going to take us 9 shots or even 7, but we're not totally confident because we haven't done it yet. So we won't really know until."
Such a complicated vaccine will take a huge amount of testing in more than a dozen clinical trials. All this testing will be very expensive and time-consuming, Schief points out.
That's where the mRNA technology comes to the rescue. Vaccines made with the mRNA technology have immense flexibility. They can be tweaked, tinkered with and optimized very easily. If scientists want to change the shape of the vaccine a tad, it's super easy.
"For an [m]RNA vaccine, the process will be much faster and cost much less," Schief says. "I don't want to say cheap because it's not. It's still not cheap, but it's a lot less expensive to make the [m]RNA."
So serendipitously, the COVID pandemic greatly accelerated the development of this experimental vaccine, and in many ways, actually made it plausible. Because the pandemic pushed researchers and pharmaceutical companies, who had no choice but to take a risk and test the mRNA technology in people. Within a year, they proved the technology not only works but actually works really well, Schief says.
"We didn't know before COVID that mRNA technology was going to be as safe and as effective as it has proven to be," he says. "The mRNA vaccines induce really good responses."
So this past January, the International AIDS Vaccine Initiative, along with National Institutes of Health and Moderna, launched the first clinical trials of an mRNA vaccine for HIV.
After nearly 40 years of trying, researchers are optimistic about having an approved vaccine in the near future. "Because technology has come so far now," says Derseree Archary in Durban, South Africa. "I know this experimental vaccine sounds like science fiction, but I think in the next 5, 6 years, we should have a vaccine, hopefully, that may be able to confer some degree of protection against HIV."
Back in Los Angeles, Dr. Jesse Clark is helping to lead one of the trials at UCLA's Vine Street clinic in East Hollywood, which also helped to test Moderna's COVID vaccine.
While chatting with Clark at the clinic, I can see how proud he is to be a part of this historic trial.
"I actually went to medical school to be an HIV specialist," says Clark, who also directs the UCLA South American Program in HIV Prevention Research program in Lima, Peru, and Rio de Janeiro, Brazil. "I wanted to help people that other people didn't seem to really want to help that much, partly because I could see myself in them and also just because they needed help."
