Promising new HIV vaccine candidate trialled in humans
Researchers have been trying for decades to find a vaccine for HIV.
Several candidates have made it through initial rounds of clinical trials, only to prove ineffective at generating an immune response in humans.
But a new vaccine candidate is the fifth ever to make it through to the so-called 'phase 2b' trial stage.
Dr Dan Barouch
Professor of Medicine at Beth Israel Deaconess and Harvard Medical School in Boston
Dr Norman Swan
Norman Swan: For 35 years since the HIV AIDS epidemic took hold, scientists have been searching for a vaccine. It's been formidably difficult because of the virus's ability to evade the immune system. And in the last three decades only four vaccines have been good enough to get into large-scale human trials. Unfortunately it didn't work well enough or well at all, but now the fifth candidate vaccine is being studied and shows more promise, according to a paper just published in the Lancet. Earlier today I spoke to one of the scientists, Dan Barouch, who is Professor of Medicine at Harvard Medical School in Boston.
Dan, thank you very much for joining us on the Health Report.
Dan Barouch: My pleasure.
Norman Swan: What's different about this vaccine compared to others that have been tested with variable results?
Dan Barouch: The first one is that it uses a potent viral vector, the adenovirus that brings HAV antigens into cells, and that hasn't been tested before. And the second thing that's different is that it uses mosaic antigens. What I mean by that is that the HIV sequences in the vaccine are not from any one single HIV strain but rather the sequences are small bits from many different HIV strains. The goal is to raise immune responses that are relevant for a larger number of HIV viruses worldwide.
Norman Swan: So you've got a cocktail essentially of different forms of the human immunodeficiency virus.
Dan Barouch: It is a cocktail, but many of the different pieces are stitched together.
Norman Swan: So what evidence did you have in animals before you went to humans in this that it actually could work?
Dan Barouch: In monkeys the vaccine was highly immunogenic, and also provided 67% protection against challenge with an AIDS like virus in monkeys.
Norman Swan: And when you say immunogenic, it means it induced an immune response.
Dan Barouch: Yes.
Norman Swan: And then you did a trial in 400 people in Africa.
Dan Barouch: Yes, we did a phase 1/2a clinical study in 393 individuals in the United States, East Africa, South Africa and Thailand, and the vaccine also raised robust immune responses in humans. The responses in humans were very similar to the responses in monkeys.
Norman Swan: A phase 1/2a trial is to test safety in humans and also to start working out the dose. The dose seemed pretty high to me and maybe impractical. You have to give a lot of different injections to get this response.
Dan Barouch: The vaccine was a series of four injections given at months zero, three, six and 12. We are doing some additional clinical studies to look at shortened regimens and down to three immunisations.
Norman Swan: When you do a trial in humans you can't challenge people with HIV.
Dan Barouch: Of course not. The main finding from the current paper is that the vaccine was safe and induced robust immune responses in both humans and monkeys. And because of the protection in monkeys and the safety and immune responses in humans, this vaccine candidate has been advanced into a larger scale study which is called a phase 2b clinical efficacy study which will determine whether the vaccine will prevent HIV infections in humans in southern Africa.
Norman Swan: In other words, what you're doing is observing the population in a high prevalence area and seeing what they do compared to controls.
Dan Barouch: Correct. The study is in 2,600 young women in southern Africa.
Norman Swan: Why women?
Dan Barouch: Because young women is one of the highest risk groups in that region of the world. The way that the study is conducted is that it's a randomised and blinded study and placebo-controlled study, so half the women get the vaccine, half the women get placebo. All participants are given the best medical care available as well is the best HIV prevention advice, so everyone benefits. But yet unfortunately, despite our best efforts, some infections still will unfortunately occur. And then several years later we will be able to see if there's a decreased HIV incidence rates in the vaccine group compared with the control group.
Norman Swan: The last vaccine to show promise was in Thailand and it showed a 33% or around about a 33% protection rate which was considered too low to be practical. If you manage to achieve the 67% or thereabouts, in other words two-thirds, that you saw in monkeys and humans, is that going to be enough for a vaccine out in the field?
Dan Barouch: Well, it's a difficult question because it will depend on the prevalence rates, the state of the epidemic at that time, the desires of public health authorities, so it's difficult to answer at this point in time. But what is clear is that the more effective the vaccine is, the more likely it will be in a position where it will be endorsed.
Norman Swan: One of the challenges with human immunodeficiency virus is that it changes its spots regularly. You've tried to deal with this by creating this cocktail of different viruses, but you haven't got closer to what is the Holy Grail which is the core piece of HIV which you could immunise against. How robust do you think this is to changes in the human immunodeficiency virus?
Dan Barouch: You hit on one of the major challenges of HIV vaccine development which is virus variability and the ability of a virus to mutate quickly to evade immune responses. The mosaic strategy at least partially addresses that challenge. Is it a perfect solution? No, of course not, nothing can be a perfect solution. But it does increase the relevance of the immune responses to be reactive against more strains worldwide. This is only the fifth HIV vaccine concept that will be tested for efficacy in humans in the 35-year history of the global epidemic. So there's not a lot of vaccine candidates that have made it to this point in testing. So I think we are happy with the current results, we are cautiously optimistic, but we can't assume that this vaccine will work in humans until the clinical efficacy trials are done.
Norman Swan: It's a complicated vaccine. Is it going to be affordable if it works?
Dan Barouch: The cost of the vaccine is not yet known and will be determined at a later point in time. But certainly all the partners and stakeholders are very cognisant of the fact that the vaccine has to be affordable for the people who need it.
Norman Swan: Dan, thank you very much for joining us on the Health Report.
Dan Barouch: You're very welcome.
Norman Swan: Dan Barouch is Professor of Medicine at Beth Israel Deaconess and Harvard Medical School in Boston.