Scripps Research Part Of HIV Vaccine Breakthrough

Speaker 1: 00:00 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 trials results are the first step toward realizing that goal. Johnnie Mae is William sheaf, a professor and immunologist eScripts research and executive director of vaccine design at [inaudible] neutralizing antibody center and professor congratulations. Thank you very much. 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 and nearly 2 million new infections each year. So give us a sense of how important it would be to have a vaccine prevention for HIV. Speaker 2: 01:03 You know, it's something like between four and 5,000 people every single day, get newly infected with HIV and, uh, here in the United States and in the developed world, people have access, you know, through their insurance. Basically two drugs can PR that can save you from HIV, that you can 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 their social and economic barriers to access. And if you don't have access to those drugs and you get infected, there is no, there's no known cure. There's no way to get rid of the virus. And so it's still basic. It is really a death sentence for many people still, and a vaccine would be the way, uh, if we could make a vaccine, it would, could prevent infection and prevent, uh, millions of people every year from having to fight this battle for the rest of their lives. Speaker 1: 01:58 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. Speaker 2: 02:08 Yeah. So people are, I think everyone is getting pretty used to hearing about the spike protein of Corona virus 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 well, and people are used to hearing about the variants now of Corona virus. And in some cases, variants make the vaccine protection, you know, 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, you know, 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. Speaker 1: 03:08 Vaccine trials 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? Speaker 2: 03:20 Yeah, that's a good question. So we, we, we believe, and 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. Um, 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, uh, when you're designing a vaccine, when the vaccine is first exposed to a person, it first engages with what are called naive B cells. And it turns on a set of naive B cells. And 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 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 they are, 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. Speaker 1: 04:34 And when you stimulate the right B cells, then you can develop these broadly neutralizing antibodies that can keep up with this mutating viruses. Speaker 2: 04:44 Well, yeah, the idea actually is to be ahead of the mutating virus. Uh, the idea is not so much to keep up, but to illicit 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 and the in the clinical trial that we just carried out. You know, we were not eliciting broadly neutralizing anybody's, but we, 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 followed in six, to be given in succession that will allow the B cells to develop further and produce antibodies that are actually broadly neutralizing antibodies. Speaker 1: 05:33 So a series of vaccinations would produce the right antibodies. Speaker 2: 05:37 That's the goal. Yeah. Starting with the one we just tested and then a series of a few additional ones that are different from the one we just gave. Speaker 1: 05:46 Now you presented your team's results yesterday to the international AIDS society research conference. Was this clinical trial more successful than you anticipated? Yeah, so we were testing Speaker 2: 05:58 A new vaccine concept and no one had ever tested this in humans before we had shown a relatively good results in animal model systems, but we didn't really know if it would work in humans. Um, and we also thought even if it does work, we would be happy with a proof of principle, not necessarily, uh, such great performance that we could just build on it and keep, and just use this particular vaccine antigen. You know, you can always imagine if you prove the principle, then you say, okay, now we need to make it work better so that we can really use this in the real world, but it actually performed well enough that we don't need to go back to the drawing board and improve it at the moment we can just build on it and the long run, we might try to improve it, but it worked pretty darn well. So yeah, we were surprised at how well it worked, both the concept and the sort of the practical performance. Speaker 1: 06:49 You mentioned the similarities between the spike proteins that we've been hearing about on COVID-19 and the spike proteins in the HIV virus. I'm wondering, where is the crossover here? What other diseases might a vaccine like this be able to prevent? Speaker 2: 07:06 Yeah. So this strategy we're actually looking into using this strategy to induce broadly neutralizing antibodies against Corona virus is also a, and that again would be not to not to, uh, 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. Uh, so we're looking into trying or investigating whether this strategy might help elicit broadly neutralizing antibodies against Corona viruses. We and others are working on trying to make what's called a 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 enlisted really broad neutralizing anybodies. And there's some reasons to believe that the strategy that we just tested for HIV might help in that quest. And there are other, there are other viruses as well. Dan gay and Zika. We may, we may be able to use with the strategy for Speaker 1: 08:04 What happens now, how does the research proceed to the next? Speaker 2: 08:08 Actually people have heard of the modern, a vaccine for Corona viruses, and we've been collaborating with Madonna 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 our, if the same vaccine concept will work as delivered by Madonna M RNA. And we're 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, uh, broadly neutralizing antibodies. And so we have another clinical trial that's planned to start later this year, actually. Speaker 1: 08:48 Okay. Unfair question. When do you think this series of HIV vaccinations might be available to Speaker 2: 08:53 The public? I mean, you know, we're 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 our, all of our colleagues. How soon might it 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 did, maybe, you know, just a few years later, uh, but I would say it would be hard to imagine having a real vaccine for HIV before, let's say 10 years from now. Speaker 1: 09:45 Okay, then William shoot. Thank you so much. William chief is a professor and immunologist as scripts research and executive director of vaccine design at [inaudible] neutralizing antibody center. Thanks so much. And thanks for your Speaker 2: 09:58 Work. Thanks very much, Maureen. Speaker 3: 10:07 [inaudible].