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Scripps Research Moves One Step Closer To Vaccine To Prevent HIV

An undated computer image of the outermost layer of HIV.
Courtesy of Sergey Menis, IAVI
An undated computer image of the outermost layer of HIV.

There’s been a major breakthrough in the fight against HIV which also may change the way vaccines are used to fight other diseases. Scripps research has announced success in the first-clinical trial of a new approach against the disease, one that involves vaccines that boost the body's ability to produce antibodies. Researchers have been working for 40 years to find a key that would unlock the riddle of HIV prevention. This clinical trial’s results are the first step toward realizing that goal.

Scripps Research announced what it’s calling a major breakthrough in the fight against HIV. The method may also change the way vaccines are used to fight other diseases.

The research organization said it had success in the first clinical trial of a new approach against HIV, which involves vaccines that boost the body's ability to produce antibodies.


Researchers have been working for 40 years to find a key that would unlock the riddle of HIV prevention. The results of this clinical trial could be the first step toward realizing that goal.

William Schief, a professor and immunologist at Scripps Research and executive director of vaccine design at IAVI Neutralizing Antibody Center, joined Midday Edition on Thursday to discuss the trial’s findings and what’s next. Here’s a lightly edited transcript of a portion of that interview:

Q: The world has been so focused on COVID, it's important to remember that more than 36 million people around the world are living with HIV with nearly 2 million new infections each year. So give us a sense of how important it would be to have vaccine prevention for HIV?

A: It's something like between 4,000 and 5,000 people every single day get newly infected with HIV. And here in the United States and in the developed world, people have access, through their insurance, basically to drugs that can save you from HIV, that you can, you know, maintain a relatively normal life even if you get infected. But in many places around the world, access to those drugs is not so easy -- they're expensive, they're hard to get, there are social and economic barriers to access. And if you don't have access to those drugs and you get infected, there is no known cure. It really is a death sentence for many people still. And if we could make a vaccine, that could prevent infection and prevent millions of people every year from having to fight this battle for the rest of their lives.

Q: One of the reasons that an HIV vaccine has been so elusive is the complexity of the virus itself and its ability to mutate. Tell us about that.


A: I think everyone is getting pretty used to hearing about the spike protein of coronavirus and how all the different vaccines are trying to elicit antibodies that bind to the spike protein and block it from infecting ourselves, and HIV has a similar spike protein. And people are used to hearing about the variants now of coronavirus. In some cases, variants make the vaccine protection more difficult to achieve, and HIV is just that problem on steroids. It's really not one virus, it's like 50 million different viruses, all of which have a different spike protein or variants of the spike protein. So if you make a vaccine using one spike protein of HIV, you might protect against that particular variant, but not against the other 50 million that are circulating around the world. So the real challenge is to induce what we call broadly neutralizing antibodies that have the ability to neutralize diverse strains of HIV -- and that is an incredibly difficult problem.

Q: This vaccine trial showed success in stimulating production of rare immune cells that could eventually produce a rare type of antibody. What do you mean by rare immune cells?

A: We know that we need to induce what we call broadly neutralizing antibodies. Those are antibodies that bind to patches on the HIV spike that don't change very much. It's just very difficult to elicit those kinds of antibodies. Those antibodies that can broadly neutralize HIV have special properties typically. And when you're designing a vaccine, when the vaccine is first exposed to a person, it first engages what are called naive B-cells and it turns on a set of naive B-cells. Those B-cells will mature and gradually learn how to neutralize the virus. And so in our vaccine clinical trial, we had a strategy to target a very specific set of naive B-cells that have genetic and structural properties that give them the potential to develop into the kind of antibodies that we know we need to elicit in the long run and rare. They're rare because their frequency is about one in a million of naive human B-cells. So the vaccine had to find, sort of like a needle in a haystack, and activate the right B-cells, and it seems to have done that.

Q: And when you stimulate the right B cells, then you can develop these broadly neutralizing antibodies that can keep up with this mutating virus. Is that it?

A: The idea actually is to be ahead of the mutating virus. The idea is not so much to keep up, but to elicit an antibody that doesn't mind if the virus is mutating because it knows where to hold on, where the antibody is not making any mutations. And the idea in the clinical trial that we just carried out, you know, we were not eliciting broadly neutralizing antibodies, but we were eliciting precursors to broadly neutralizing antibodies that had some key properties that are required for one particular kind of broadly neutralizing antibody. And the challenge for us now will be to develop additional shots to be given in succession that will allow the B-cells to develop further and produce antibodies that are actually broadly neutralizing antibodies.

Q: You mentioned the similarities between the spike proteins that we've been hearing about on COVID-19 and the spike proteins in HIV. I'm wondering where is the crossover here? What other diseases might a vaccine like this be able to prevent?

A: Yeah, we're actually looking into using this strategy to induce broadly neutralizing antibodies against coronaviruses also. And that, again, would be not to catch up to the coronavirus variants, but to be ahead of it, and to elicit antibodies that really don't care which variant the coronavirus generates, it can neutralize no matter what. So we're investigating whether this strategy might help elicit broadly neutralizing antibodies against coronaviruses. We and others are working on trying to make what's called the universal flu vaccine, which would be the same kind of idea, elicit broadly neutralizing antibodies against flu. You wouldn't have to take a new vaccine every year if we elicited really broad neutralizing antibodies. And there's some reason to believe that the strategy that we just tested for HIV might help in that quest. And there are other viruses as well, dengue and Zika, we may be able to use the strategy for.

Q: So what happens now? How does the research proceed to the next step?

A: People have heard of the Moderna vaccine for coronaviruses and we've been collaborating with Moderna for quite a long time and our major interest is that with their technology, we can do more clinical trials more quickly. So we actually are going to go back into humans and test if the same vaccine concept will work as delivered by Moderna mRNA. And we are going to test the first try at giving a second shot. So the next shot of our vaccine that's supposed to have the antibodies develop more toward broadly neutralizing antibodies. And so we have another clinical trial that's planned to start later this year.

Q: When do you think this series of HIV vaccinations might be available to the public?

A: I mean, we're trying to go as quick as we can, but it is a very, very difficult problem. It's probably the most difficult vaccine problem ever attempted, which is why, as you said at the beginning, it's been 40 years and we still don't have a vaccine. And a lot of smart people have tried a lot of clever strategies. So will this ultimately work? You know, we can't say that it will. We're going to do our best with all of our colleagues. How soon might work? I mean, if everything goes really well and, you know, we might be able to see, I would say, in the next five years that we can induce broadly neutralizing antibodies against HIV. And then when could that be deployed as a vaccine around the world? You know, if we went as fast as the COVID-19 did, maybe, you know, just a few years later. But I would say it would be hard to imagine having a real vaccine for HIV before, let's say, ten years from now.