IRA FLATOW: This is Science Friday. I’m Ira Flatow. One of the most striking parts of the COVID-19 pandemic has been the rapid development and deployment of highly effective vaccines, especially those based on mRNA, a technology that hadn’t been widely used in vaccines before. Now, researchers are working to see what other illnesses that mRNA technology might be used for.

And recently, several trials began, early phase I human trials, for an mRNA-based vaccine for HIV, the virus that causes AIDS. Joining me now is Dr. Anthony Fauci, director of the National Institute of Allergy and Infectious Diseases in Bethesda, Maryland. An NIH-supported trial of three different HIV vaccines using mRNA technology recently got underway. Welcome back to Science Friday.

ANTHONY FAUCI: Thank you, Ira. It’s good to be back with you.

IRA FLATOW: Thank you. Now, researchers have been trying for an HIV vaccine for so long. I’m sure you know that. What makes you think that this approach will be more successful?

ANTHONY FAUCI: Well, it almost certainly is related to the spectacular success that we’ve seen with the utilization of the mRNA platform and its great deal of flexibility of expression in the arena of COVID-19. We went from the sequence of the SARS-CoV-2 virus and, within 11 months from the publication publicly of that sequence, we have vaccine going into the arms of individuals that has already been proven to be safe and effective.

So because of that, investigators are all now putting a considerable effort to determine if whatever advantage one might get– the flexibility, the ability to express different antigens and different conformations– if we can somehow transfer that to the very problematic field of HIV vaccine, that certainly would be worth trying. And that’s exactly what we’re seeing in the trials that NIAID is funding in a phase I level to look at different conformations of HIV envelope antigens to be expressed in an mRNA platform, with the hope that we get similar results. So it’s an exciting field. It’s really been triggered and stimulated with a considerable amount of enthusiasm, based on the success with SARS-CoV-2.

IRA FLATOW: Well, let’s talk a bit about that. How much does what we learned with SARS-CoV-2 apply to these new vaccines, or is it a completely separate product?

ANTHONY FAUCI: Well, it’s a separate product in that the immunogen is different. What’s the similarity, Ira, is the platform that’s used. If one thinks in terms of the two major components of a vaccine, it’s the vaccine platform– and that could be mRNA, that could be viral live particle, that could be nanoparticle, that could be vector expressed, like adeno– and then the other component is the actual immunogen design. So we have the platform itself, but then the immunogen design of SARS-CoV-2, namely the stabilized prefusion spike protein of SARS-CoV-2, combined with the flexibility of the mRNA platform, led to the success of that.

That’s the same sort of approach that’s going to be applied to the HIV translation of that concept, where you’ll have an mRNA and you’ll have various conformations of envelope and other proteins of HIV to be used in the mRNA. So hopefully, what we’ve learned with SARS-CoV-2, there’s a lot of enthusiasm and some cautious optimism that that might push the envelope a bit and get us a step closer to an HIV vaccine.

IRA FLATOW: Yeah, because last time we talked about the difficulties of creating an HIV vaccine, if I recall it correctly, you said that one of the problems is that the virus mutates too much to keep up with it. It’s sort of like whack-a-mole. If that is correct, how does this technique keep up with the change in the virus?

ANTHONY FAUCI: The problem with an HIV vaccine is, in many respects, related to the fact that the body, at least the way the immunogen is presented to the body, does not do very well in making broadly neutralizing antibodies, which is essentially the sine qua non of what you would need to get a safe and effective HIV vaccine. We’ve been able to induce, with a variety of products, binding antibodies, antibodies that might be neutralizing against just the autologous strain.

But thus far, despite years of trying, we’ve been unsuccessful to induce a sustained broadly neutralizing antibody response that, given the ability of this virus to change so much, you want something that is broadly neutralizing against any iteration of the particular virus. That’s really been the stumbling block of getting an HIV vaccine. So it’s hoped that, with this new manner of presenting the immunogen to the body with the mRNA technology, that that might be the extra added step that would get us a little bit closer to a successful HIV vaccine. It’s a complicated issue, but we believe it’s one way to get closer to that possibility.

IRA FLATOW: Yeah, you seem to be giving us some caution flags here not to expect too much. Would I be reading that correctly?

ANTHONY FAUCI: No, you’re actually reading it correctly, Ira, because HIV has been such a problematic situation to develop broadly neutralizing antibodies, to get the body to coax the immune system along to make antibodies that are truly broadly neutralizing. I mean, any antigen will induce an antibody. I mean, that goes without saying. The trick with HIV, given the nature of that virus, if you really want protection, it’s got to be a broadly neutralizing antibody. And we’ve not been able to do that.

So when you hear a degree of caution in my explanation, it’s because I am aware of really how difficult it has been through multiple attempts to get the engagement of the B cell repertoire to come up with a broadly neutralizing antibody. But again, like I said, that combination of a new platform that’s shown success with SARS-CoV-2, together with some clever immunogen designs with the right structural conformation, might get us to that goal post. I hope so.

IRA FLATOW: OK, so we’re in phase I. Phase I means what? We’re just trying to see that it doesn’t hurt people?

ANTHONY FAUCI: Well, one, it’s safe, and does it induce the kind of immune response that you’re hoping for. It has nothing to do with efficacy because you don’t know until you do a trial that’s large enough to determine efficacy. So when you’re dealing with a phase I, it’s just as you say, Ira. A, is it safe? Are there any idiosyncratic or difficult reactions? Are there a lot of reactogenicity? Are there any adverse events?

And two, you’ll get the opportunity to measure the antibodies that are induced in the phase I response. And you could get an inkling of whether or not they do have a degree of broad reactivity to them. You don’t necessarily, in that trial, show that it works, but you can get a hint if you’re dealing with the induction of what looks like broadly neutralizing antibodies, or at least a step towards broadly neutralizing antibodies.

IRA FLATOW: OK, so then how long do you think it will take before we know whether we move on to phase II or not?

ANTHONY FAUCI: Well, phase Is really don’t take very long. They’re really measured in months, if you want to call it that, because usually any adverse events or reactogenicity you see pretty quickly. And it usually takes when you give it a period of at least several weeks to more than that, months or so, to determine the level of the immune response. Once you get that, if you get favorable data, then you start thinking of expanding the numbers of people in the trial to get a little bit more information not only about the safety, not only about the immunogenicity, but then you could start talking in terms of the possibility of some early inklings of efficacy.

IRA FLATOW: And then, of course, hopefully you’d move on to phase III, which is actually testing out.

ANTHONY FAUCI: Exactly, a much, much larger trial to really nail down efficacy.

IRA FLATOW: Given the speed at which COVID was, as you say, the short months-long period, could we expect to see a months-long instead of a years-long period of the test of the HIV vaccine?

ANTHONY FAUCI: Probably not, Ira. The reason we were able to do it so quickly with SARS-CoV-2 is that we were testing it in tens of thousands of people in the middle of an explosive outbreak. And when you have an explosive outbreak, you’re going to get a lot of endpoints very quickly.

That’s not necessarily the case because, although HIV, in certain subpopulations, has a high degree of incidence, it isn’t anything like what we saw in the explosive outbreak of SARS-CoV-2, which was spread by the respiratory and really had no other way of blocking it. Whereas with HIV, what you’ve got to do if you want to do an ethical clinical trial, you’ve got to instruct people in the use of condoms. Some of them even want to be using, and it’s appropriate to use pre-exposure prophylaxis.

So to get endpoints in a HIV vaccine trial when you have, in many respects, the ethical obligation to let people know and make available to them what they can do to avoid infection, that is very difficult, and very different, as it were, from an explosive respiratory illness, in which you don’t really have much protection except wearing a mask.

IRA FLATOW: Hm. So you’re saying you have to be very particular in how you choose the people to go into the trials.

ANTHONY FAUCI: Right. You really want to do it in a group that’s relatively high risk, because if you do it in a very low risk, by the time you get enough endpoints of infections or protection from infections, it could be a matter of years and years. And that’s the reason why I answered your question that I don’t think it’s nearly going to be as quickly as the result that we got from the SARS-CoV-2, which was really measured in a matter of months.

IRA FLATOW: Do you think you’re going to have trouble finding enough people for the trials?

ANTHONY FAUCI: That’s the reason, Ira, why many of the vaccine trials that have been conducted have been conducted in other countries, because in the United States, the incidence even in at-risk populations is still, relatively speaking, rather low. So if you really want to get an answer, particularly if you want to get an answer in a reasonable period of time, you’ve got to go to a place where the risk and incidence is relatively high.

IRA FLATOW: I’m Ira Flatow, and this is Science Friday from WNYC Studios. I can’t let you go in the last minute or two that we have without talking about COVID for a moment, because according to the CDC reports, about a third of Americans have not gotten their initial round of shots and more than 70% have not received boosters. Do you find that incredible?

ANTHONY FAUCI: That’s very, very unfortunate, in my mind, Ira. We have a highly effective and safe vaccine, and we have only about 65% to 67% of the total population is fully vaccinated. Of those who are vaccinated, about 50% of them have received their boost. That’s really a very low number. We’ve got to do much better than that, particularly given the data, which are extremely convincing, of the difference between vaccinated and unvaccinated and vaccinated with a boost compared to unvaccinated when you look at the incidence of hospitalization, severe disease and deaths.

As a country, a developed, rich country, we are not doing nearly as well as so many other countries, including several in Europe and the UK, when it comes to the percentage of the population that’s both fully vaccinated as well as boosted. We’ve really got to do much better. The reasons for that, Ira, are very complicated. It has a lot to do with the extraordinary degree of divisiveness that we have in this country, where vaccination has become, in some respects, politicized. And there’s been a lot of pushback and a lot of anti-vaccine sentiment in the country. Really quite unfortunate when you’re dealing with an outbreak that has already killed close to 1 million Americans in two years and three months.

IRA FLATOW: And Congress seems to be reluctant about giving more money. President Biden requested billions of dollars for tests and treatments, and it’s sort of stalled in Congress right now.

ANTHONY FAUCI: Yeah, it is. And again, that’s another really unfortunate situation. We were thinking we were going to get a rather large amount, I mean, well over 30 billion, and then it went down to 22. And then 15 billion went into the omnibus, and then it was yanked out. So unless we get some money pretty quickly, Ira, we’re not going to be able to finish some of the trials that we started, and certainly not initiate anything new, unless we get rescued here with some resources that can have us continue our efforts.

IRA FLATOW: It almost seems like we’ve gone back to a pre-COVID mentality.

ANTHONY FAUCI: Well, I don’t know if you want to call it that, but it certainly is something that’s not good. That’s for sure.

IRA FLATOW: Yeah. And finally, almost lost in the talk about COVID survivability– we have talked about them in depth– are the long haulers. People who are infected, come down with long-term illnesses or disabilities. And I get the impression that people think that, well, I’ve gotten COVID, I’ve survived it, I’m free and clear. But there could be a lot of cases of long haulers that don’t show up yet.

ANTHONY FAUCI: Yeah, that’s the truth, Ira. That’s one of the reasons why we are concerned not only about hospitalizations and deaths, but also, you know, it’s a range. It’s anywhere from 5% to 30% or so of individuals who, to a greater or lesser degree, have the lingering of signs and symptoms, some of which are really unexplainable by any identifiable pathogenic process, that can go on for weeks to months. Some of them are mild to moderate, but some of them can be incapacitating. And we have a number of examples, I mean countless examples of people whose way of life has been really impeded dramatically, not by the COVID that they’ve survived, but by the long COVID and the lingering on of a lot of unexplainable symptomatology.

IRA FLATOW: Well, Dr. Fauci, I want to thank you for taking time to be with us today. And good luck to you.

ANTHONY FAUCI: Thank you, Ira. Always good to be with you.

IRA FLATOW: Dr. Anthony Fauci, director of the National Institute of Allergy and Infectious Diseases, based in Bethesda, Maryland.

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