amfAR, The Foundation for AIDS Research

New Frontiers in Microbicide Research: An Interview with Dr. Robin Shattock

March 2008—Robin Shattock, Ph.D., is a professor in the Department of Cellular and Molecular Medicine at St. George’s Hospital Medical School, University of London. His research team is working on developing microbicides to prevent the transmission of HIV and is also exploring new vaccine strategies. He is also a member of several international networks that focus on microbicides and vaccines. In this wide-ranging interview, Dr. Shattock discussed the state of AIDS research and described recent developments in the field of microbicides, including the amfAR-supported studies being conducted in his lab.

amfAR: How did you first become interested in HIV research?

Dr. Robin Shattock: I started working in a diagnostic laboratory when the first cases of HIV were being recognized in the U.K. in the mid to late 1980s. It was an exciting time because so little was known about this new infection, so I got involved in research. Studying HIV is not only important to global health, but it has also changed our understanding of immunology and virology in a way that no other infection has.

amfAR: When was the notion of a microbicide first floated?

Dr. Shattock: It’s got to be about 17 years ago now. I think the first product was dextrin sulfate—a sulfated polyanion. But it really was very slow to get going because at the time everybody was predicting we’d have a vaccine, so why did we need this low tech approach, which wasn’t really seen as mainstream science?

amfAR: How has microbicide research changed since you began working in the field?

Dr. Shattock: I think the field is going through a major change in approach in that it’s moving away from the first generation ideas that really came out of academic roots and that required a lot of developmental time. Now there are plenty of new-generation drugs that are relatively easy to manufacture—highly developed drugs from the pharmaceutical industry that we already have a significant amount of information about. So it’s completely changed from an academic-only approach to a partnership between the funders, the investigators, and major pharmaceutical companies.

amfAR: Are the pharmaceutical companies putting much money into microbicides?

Dr. Shattock: Not directly, although they are allowing their drugs to be used by licensing them to public-private partnerships. Perhaps the best recognized of those is the International Partnership for Microbicides. While the drug companies are not actually donating money, the investment in developing those drugs is enormous. So, in fact, in-kind contribution will run into the hundreds of millions.

amfAR: Your work spans microbicide and vaccine research. Can you speak a little bit about how they intersect and how you came to be involved in both areas?

Dr. Shattock: The reason that I became involved in both approaches is my interest in studying the earliest events in HIV transmission. To do that, one needs to understand at what point the virus can be blocked from establishing infection and also how the immune system is involved both in terms of its response to a potential microbicide and its response to the virus. In many ways it takes a similar mindset to think about that and then relate it to either chemical strategies—microbicides to block infection, or immunological strategies to block infection. Or even their potential combination.

amfAR: You have said that there might be some chance that protease inhibitors could be used as a microbicide. But protease inhibitors act after the virus is integrated into the DNA, so isn’t there some chance that there will still be infected cells that might seed infection later?

Dr. Shattock: The field is really only starting to understand how an infection is disseminated, and current hypotheses suggest that you may get a small first sign of infected cells in the mucosal environment. If you’re able to hit infected cells in small numbers hard enough with the drug, it may lead to the eradication of that infection as the cells die out either naturally or through immune response. Clearly, we need to test that concept. We have laboratory data at least showing that protease inhibitors can block infection of mucosal tissue. And we hope to directly look at that in animal challenge studies.

amfAR:  Can you talk about the difficulties that young scientists face in terms of establishing themselves in the field of AIDS research?

Dr. Shattock: For me, that is of vital importance. Science does not have a clear or easy career development path. While it takes a lot of effort to get a Ph.D. and become a post-doc, the highest level of attrition of scientists from the field is at the post-doc level. And that is because it is very hard to transition from being an investigator in the laboratory to actually being able to get your own peer-reviewed, funded work established. So the amfAR fellowships play a vital role because they allow individuals to take that transitional step, to have some funding that they can call their own. They can prove themselves with that, and use it as leverage to get more grant funding and to get on the tenure-track career level. Without that kind of approach, we lose the best scientists.

amfAR: What has been your experience with mentoring young researchers?

Dr. Robin Shattock:  I find it very rewarding. It’s just wonderful to see people develop new skills, start to be able to generate ideas. Well, generating ideas is not hard, but generating an idea and converting it into something that people will then fund is very hard. And to see someone go from having no understanding of how to do that to being able to get their first grant and then get more funding—to see someone’s excitement in the field grow along with their confidence—is a great thing.

amfAR: There seems to be some pessimism about the future of vaccines, especially after the recent failure of the Merck vaccine trial, which was halted because of data showing that the potential vaccine was not only ineffective in preventing HIV, but that more new infections occurred among volunteers taking the drug. Are you more optimistic about the prospects for developing a microbicide than you are about vaccine research?

Dr. Robin Shattock: I think the first point is that when you’re trying something, failure is part of it. In terms of microbicides, I think they will be easier to develop and test in a timely fashion than vaccines. I think in the next five years we may see a product that definitely reduces transmission by a measurable amount, and by that I would say there has to be upwards of a 60 percent reduction in risk. But that won’t be the end; that will just give us clues to develop better microbicides.

Microbicides will prevent infections that are ongoing, but probably they will not be sufficient to reverse the epidemic. That will ultimately require either treatment that leads to a cure or a protective vaccine.

In terms of vaccines, there have been some major setbacks that have been quite disappointing. But they’re still improving our understanding of what it will require to make a vaccine. So it’s been a wakeup call; it’s been a moment of perhaps greater realization that we really need to come up with novel concepts. But you never know what somebody will discover tomorrow.

amfAR: So what about a cure?

Dr. Robin Shattock: Well, it would be a fantastic thing to have. I think it’s something worth shooting for. Do I have high expectations that something could be realized in the near future? No. Do I think it’s impossible? No, I think it is possible. Not with current technology, perhaps, but as with vaccines and microbicides, the goal of developing a cure is worth pursuing with a concerted research effort.