Wayne Koff, chief scientific officer at the International AIDS Vaccine Initiative (IAVI), spoke in an interview about the challenges in developing a vaccine for one of the trickiest and deadliest known viruses, how scientists are getting closer to developing a vaccine for human immunodeficiency virus (HIV), and what makes India attractive for vaccine development. Edited excerpts:

Is there progress in developing an HIV vaccine?

I think in the last three or four years, we’re really in a renaissance period for the HIV vaccine. I say that for three reasons. One, we have had the initial evidence of the efficacy of a candidate vaccine in a clinical trial, albeit it only protected only a third of the volunteers, so we know we have to do better. (These results came out in 2009 in Thailand, the trial for RV-144.)

So that was one set of evidence and beginning next year, there will be another round of efficacy trials in South Africa of similar candidates to see if they can improve upon the efficacy from 30-31% to licensure level of 50-60%. We should have data in three years or so after the beginning of trials.

The second point is in monkeys, the animal models for the HIV infection, there have been a series of candidates which have shown improvements in the animal models compared to the initial generation of the candidates, and those new candidates will soon be entering into clinical trials. Finally, the greatest advance in the last three or four years is really our identification of broadly neutralizing antibodies in HIV.

So, they’re all different around the world. Our colleagues felt that really to produce a safe effective AIDS vaccine, we require the induction of broadly neutralizing antibodies. Our colleagues have found a large number of neutralizing antibodies against HIV. We use these as tools to identify where on the region of the virus are they binding. As a result of that, we know the small number of regions, which are the targets for broadly neutralizing antibodies, and these are the targets for which the emphasis is ongoing.

How has the approach to develop HIV vaccines changed?

It is almost the reverse engineering of vaccines. So, if you think about how vaccines were made a long time ago, they were empirical, it was mostly trial and error. You would identify the pathogen, you would either weaken it or you would inactivate it. And that would be the basis of the vaccine. That was how you got your polio vaccine, it was live attenuated. In case of HIV, you can’t really do that because, again, the variability of the virus. If you weaken it, it figures out a way to strengthen itself, so we have to use a molecular means. So, what we do is, we look for individuals who are HIV infected, we look into their blood to see if they have these antibodies that are neutralizing, we see if they are broadly neutralizing and, then, we isolate the antibodies and we identify the targets.

There are media reports of a variant of HIV in Cuba, which is twice as aggressive as the normal one. How has the aggressiveness of the virus changed over the years?

If you look over the years, and if you look at the aggressiveness of the HIV, I think there is a bell shaped curve. There are some viruses which are more aggressive, some are weaker than the others. The key is that from a vaccine point of view, we have to block infection with whatever strain of the virus. We have to ensure that if we make a vaccine, it is a universal vaccine. So that if you’re infected with or exposed to any virus, these antibodies can react against it.

What can we expect from the Human Vaccines Project?

One of the things we’ve learnt over the years is the vaccine industry has been extremely successful in making a large number of vaccines. But the kind of diseases we haven’t made vaccines for, like Malaria, Tuberculosis, cancer, these are complex diseases. They either are variable like HIV, or they have learnt to evade the immune system. So there is a lot of work going on in the product development space against each one of these diseases. But there are common, what we call, trans-vaccinology issues, which are common to a lot of these pathogens for which we are making vaccines.

What kind of issues?

Well, for example, a smallpox vaccine is life long, but in the US now, we have a whooping cough epidemic because its vaccine is not a durable one, and there is a mumps epidemic because the vaccines are not durable. Another issue is the population differences. There are some vaccines that work well in the young, but they don’t work as well in the elderly where they are needed, like the influenza vaccine is an example which is not very effective in the elderly. So, we identified these common issues. And another issue is that the animal model is not as predictive as we hoped they are. So we wrote a paper in Science a year-and-a-half ago about how we can accelerate vaccine development. We need to focus on a lot of these trans-vaccinology problems and some point along the way, with that understanding, it should improve our probability of successfully being able to make vaccines against malaria, TB, HIV. So the idea is to create a new initiative which is likely to align major vaccine companies with the specific objectives of solving these problems. We’re now beginning to finalize the scientific plan and the business plan to be able to launch this vaccine project later in the year.

Will there be a focus in India?

We look at the initiative as a global consortium, with the core of academic centres in US, Europe, in Asia. We have been in discussions with a number of institutes and a number of ministries in India because this could lead to an acceleration in vaccine development. There’s a lot of interest in the concept. And we expect that there will be linkages and alignments. There’s a lot of excellent science in India. There are some vaccines which are less effective here as they are in Scandinavia—we’d like to understand why. One can envision a number of small clinical trials in India. We’re looking to do a large number of small clinical trials, and India has a fabulous manufacturing industry for vaccines. So there is a lot of opportunity here.

India also has terrific expertise in the computer industry, informatics and structural biology and such. And we’ve done clinical trials in India. With the population as diverse as India is, there is tremendous science, and we’d like to align with that.

Is there a time frame for when we can see an HIV vaccine?

Let me try and answer that in a couple of ways. One, we have the evidence of an initial vaccine candidate that is modestly effective. The clinical trials of candidates to improve upon them will begin in 2016, we’ll have the answers by the end of the 2020. If the vaccines are effective enough to protect 50-60% of the population, it is feasible that there could be a first-generation vaccine that is licensed shortly thereafter. If not, the next set of candidates will enter clinical trials which have done well in animal models. So, generally, it takes us 6-7 years from when a candidate enters clinical trial through all the safety, immunogenicity, efficacy trials; in that case, you can see a long time frame. I can see there is incremental progress, and let’s hope that it continues.

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