Q&A: An optimistic view of a ‘failed’ HIV vaccine trial
Click Here to Manage Email Alerts
SEATTLE — In January, Janssen discontinued the phase 3 MOSAICO trial because the HIV vaccine regimen it was testing did not prevent infection — the latest in a string of failed HIV vaccine trials.
But was the trial actually a failure?
Lawrence Corey, MD, co-principal investigator of the HIV Vaccine Trials Network (HTVN) and former president of the Fred Hutchinson Cancer Center in Seattle, told Healio during the Conference on Retroviruses and Opportunistic Infections that there are lessons that were learned during the trial that will help inform the next steps of HIV vaccine research.
After delivering a talk about the post-MOSAICO world of HIV vaccine research, Corey sat down with us to explain why he still expects an effective HIV vaccine at some point. His responses have been lightly edited for length and clarity.
Healio: In light of the failure of the MOSAICO vaccine trial, do you remain optimistic about the prospects of developing an HIV vaccine?
Corey: Of course I remain optimistic. You know, I’ve been at this for a while, and you have to have some optimism in research anyway.
The trial, of course, was not, quote, a failure. We got an answer. It wasn’t the answer we want, but we have a direction because of the [Antibody-Mediated Prevention (AMP)] trial. It’s very clear that these non-neutralizing antibody approaches are not going to work, so we need to move toward something else.
What we showed with AMP is that, if you give a high enough level of antibody, you can actually prevent acquisition. That is such an unbelievably important phenomenon because now we have to figure out how to make a vaccine to give those non-neutralizing antibodies.
For COVID-19, it was like falling off a log because we knew that 98% of the people, even with the first ancestral strain, would resolve the infection and be immune responsive. We knew approximately what that immune response was, we knew that we could just mimic it. So, OK, we don’t have that in HIV. But AMP established a level of neutralizing antibody. I think it’s 20- to 40-fold higher than what was required for COVID-19, but we know that that will work.
So now the issue is, how do we engineer this to make it happen? I think at this point in time, the science in HIV vaccines is just tremendously interesting and that’s why I’m optimistic. We have pecked away at it for a very long time. It is a very hard scientific challenge. As I talked about [during the conference], it is the baldest of the viruses, it’s actually the most genetically diverse, it has every diversionary mechanism we could ever think of.
But, having said that, if you make these antibodies, you prevent [people] from acquiring it. I think then that we move on to the quest of, OK, we’re very concentrated on what the target is. We have to find different targets — I think if we get two or three of them, that should be enough. It will take probably 3, 4, 5 years to get that combination and then test it enough — any of these trials take 3 or 4 years, between planning it and getting it done. So, yes, I think we will develop an HIV vaccine because we have to. You know, as much as I am into antibodies, and I think it’s great to have these long-acting antivirals. We’ve never prevented an illness on a population basis without a vaccine.
Healio: What does the timeline for an HIV vaccine look like now? Realistically, how soon could one be developed?
Corey: Being realistic, I think, in the next 5 years we need to have enough successes so we feel we can construct a vaccine that would go into a clinical trial with a reasonable sense of efficacy. And then making it, and doing the trial, is at least a 4-year phenomenon.
To me, to be honest, am I going to be head of the HVTN when that happens? No, I’m not. I’ve come to peace with that. I’m hoping to get the triple-antibodies out there. That will be an important part of choice as compared to long-acting [combination ART] and long-acting injectables.
Hopefully, I’ll be around to, sort of, revel in it, to sort of say I had confidence — it won’t be I told you so, it will be a sense of the accomplishment of American and worldwide science.
Healio: Where does HIV mRNA vaccine research stand now?
Corey: Messenger RNA is a tool, and it’s a tool because you can iterate it and we have to iterate this.
So, we’re trying to get more mRNA facilities made and to work with us on HIV vaccines. We’d love for a company to just have it as a priority. It would be great if we actually had more of an RNA resource [because] we’re having to do it ourselves. So, we’re having to create RNA manufacturing for HIV. We’re bullish on it as a tool.
What happened with COVID-19 was RNA didn’t come out of nowhere. It was 20 years (or more) in the development. It’s a tool. I’d love to see more exclusive devotion with it to HIV and see if we can build that capacity.
Healio: Many of the SARS-CoV-2 and COVID-19 successes have been built on HIV-related research. What, if anything, has HIV learned from those successes or failures?
Corey: Well, I designed the COVID-19 vaccine trials, and so, the whole infrastructure in HIV. Tony (Anthony S. Fauci, MD) called me up on March 3, 2020, and we just pivoted everything.
So, we’d like to say, has COVID-19 helped us back? MRNA would be the most obvious — and I would say it’s a hallmark gift at the moment. We need more devotion [to HIV vaccine research]. Do you expect a commercial company to do it? Probably not.
So, we’ll have to build it in academia or the public sector to get something totally devoted to fill the needs of a potential RNA vaccine, to make the immunogens that we would need to speed up the development of an HIV vaccine.
If I had a wish, I’d want to have a manufacturing team making mRNA totally devoted to HIV vaccine development.
References:
- Corey L. HIV vaccine development post-MOSAICO. Presented at: Conference on Retroviruses and Opportunistic Infections; Feb. 19-22, 2023; Seattle.
Collapse
Healio Interview.
Read more about
Click Here to Manage Email Alerts