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How Will We Finally Create a Successful Vaccine for HIV?

By Warren Tong

What Are the Biggest HIV Vaccine Obstacles?

Back in 2009, results from the RV144 HIV vaccine trial, aka the Thai trial, found that the HIV vaccine candidate in the study was about 31% effective in protecting against HIV when compared to a placebo. Though this result was modest, it was the first major breakthrough in HIV vaccine research, which renewed hope in the field. Since then, new vaccine candidates and approaches have been developed, with many more options being explored.

However, vaccine development can be a slow, challenging process. We asked some of the leading experts in the field what some of the biggest obstacles are to developing a successful HIV vaccine, and what we can do to overcome them.

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Mitchell Warren, Executive Director, AIDS Vaccine Advocacy Coalition (AVAC)

Mitchell Warren

Executive Director, AIDS Vaccine Advocacy Coalition (AVAC)

Actually, I am a big believer that the three biggest challenges we have are science, science and science. We do have some difficult decisions about what to fund and what to prioritize. But at the heart our biggest challenge in an AIDS vaccine is still about the science. There's so much we don't understand. But we're beginning to get some glimmers, so we now have this hint of why RV144, that trial in Thailand, had a positive result. Now we really need to focus and ask the question: How can we do it better? How do we develop a vaccine that's actually licensable?

The second big issue is: How do we be sure that we don't put all our eggs in one basket? That for all of the enthusiasm of the glimmers of hope we're getting, how do we maintain the discipline of funding several different scenarios at the same time? Because we all need to be planning for success, but also planning for more setback and disappointment since that's the nature of vaccine science.

Myron Cohen, Director, Infectious Diseases at UNC-Chapel Hill

Myron Cohen

Director, Infectious Diseases at UNC-Chapel Hill

I think the biggest challenge is scientific, unequivocally. The challenge is which road to pursue. Which of the things that are increasingly visible to us -- neutralizing antibodies and antibody-dependent cell-mediated cytotoxicity (ADCC) -- have a greater probability of being successful in preventing HIV with urgency?

The second issue is clinical trial design. You have to really think hard about the clinical trial design. If we make a vaccine designed to induce the response that we think is most likely to protect humans, how do we get the credible answer as fast as possible? And while we're doing that, we really need to understand surrogates of immunity. If you start injecting people with a vaccine, and you fail to see the surrogates of immunity on which it's based, you might want to have that as one of the considerations.

Nicole Frahm, Assistant Professor, Global Health at UW

Nicole Frahm

Assistant Professor, Global Health at UW

I think the one biggest one is HIV itself. It's an extremely complicated bug because it basically infects the cells of the immune system that are supposed to help you prevent an infection in the first place. So the fact that it infects CD4 cells makes it very hard to build a good immune response against it. And the other problem is that it's so diverse. To me, the problems are still mainly scientific.

But we've learned more about HIV in a very short amount of time than we've learned about any other bug in the history of infectious disease. It's really because HIV itself is so complicated that we haven't really figured out how to get a hold of it. I think that within the past couple of years, since RV144, the community as a whole has come together, both research and funders. It's a really exciting environment to be working in right now. So it's just a matter of time before we figure out how we're going to be able to deal with this.

Steve Wakefield, External Relations Director, HIV Vaccine Trials Network (HVTN)

Steve Wakefield

External Relations Director, HIV Vaccine Trials Network (HVTN)

I think the two biggest obstacles are really beginning to build a relationship with the communities where we actually conduct the research and understanding, as we move forward with combination prevention, treatment and cure research, that this all takes a very long time. The work that we have to do is going to continually take the input and education of the people who we want to participate in HIV vaccine research.

The other challenge around that is continuing to support the community-based organizations that are led by people living with HIV who can educate the public because they understand HIV in a way that the rest of the world doesn't. We actually have been blessed to have these people as the leaders in all of our advocacy and education over the years. Personally, as a person who's HIV negative, it was an HIV-positive man who taught me how to use a condom. That's the path to insuring HIV vaccine research is successful in our communities.

Jerome Kim, Deputy Director and Chief, Military HIV Research Program

Jerome Kim

Deputy Director and Chief, Military HIV Research Program

There's a certain amount of funding and coordination that's always going to be necessary. There are lots of great ideas. There are vaccines that are poised in testing. What we need is to coordinate evaluation of these vaccines in efficacy trials and the funding to do those trials. On the discovery side, we have to have adequate funding for those researchers to develop the new ideas, but also train the next generation of scientists who will take over. If you see our timelines, it's a multi-generational process. So it's about funding and coordination on the efficacy trials side. And it's about funding and education on the discovery side, so that we can follow up on all the scientific advances.

Dan Barouch, Chief, Vaccine Research at Harvard Medical School

Dan Barouch

Chief, Vaccine Research at Harvard Medical School

First, there are major scientific and technical challenges in the development of an HIV vaccine. Many of them are being overcome. Others we are working on.

A second challenge is the bigger picture of how HIV vaccines will be implemented and how they will interact with other prevention modalities. HIV vaccines don't exist in a silo, but rather as a critical part of a more complex HIV prevention field.

Bill Snow, Director, Global HIV Vaccine Enterprise

Bill Snow

Director, Global HIV Vaccine Enterprise

Our current obstacles are getting efficacy trials moving. Even the mechanics, the cost and the time that it takes just to set up a big trial of a product are daunting. People think that you can simply get some product and then have the trial. In fact, the whole business of getting the product almost needs to be started before you decide to have the trial because it takes so long. That's the period we're in now. We're in this incredibly frustrating time when we want to do the experiments and we can't yet.

Our long-term issues are, "Will the results from RV144 teach us enough to make a good enough vaccine?" And the answer to that is very likely not, though it'll get us part of the way there. What we really need to do is understand mucosal vaccines. How do we get the vaccine where it's really needed? And antibody vaccines, this is the big problem that nobody knows how to solve actually.

>Amy Chung, Researcher, Microbiology and Immunology at the University of Melbourne

Amy Chung

Researcher, Microbiology and Immunology at the University of Melbourne

I think we still don't know the immune correlates. We need to understand the immune correlates, which I think is really possible. The second thing is funding -- obviously, a key thing. Without the funding, we can't run these trials.

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