The quest for an HIV vaccine – an interview with Dr. Richard Koup

150X115_RKoup.jpgDr. Richard Koup is a senior investigator and chief of the Immunology Laboratory and Immunology Core at the Vaccine Research Center at the US National Institutes of Heath. He has been a leader in the field of understanding the role of HIV-specific T cells in the control of HIV infection and his work has helped to lay the immunological basis for the future development of an HIV vaccine. Dr. Koup is presenting the opening keynote at NCHIV 2012 and kindly agreed to talk to us about the ongoing search for an HIV vaccine.  

Could you please explain the difficulties in developing an HIV vaccine?

Developing vaccines against viruses is usually a reasonably straightforward process. Infection with many viruses, with measles for example, results in clearance of the virus during the induction of an immune response, either antibodies and/or a cellular response with killer T cells (cellular immunity). Vaccines can then be developed to induce a similar immune response. Developing a vaccine against HIV is unfortunately much more difficult. People with HIV do not clear their infections and become immune to re-infection, so this process can’t be copied. Also, there aren’t any mouse models available, as there are with other viruses. Basically all we can do is study people that have been infected with HIV and gather clues.

What types of vaccines are currently in development?

Preventative and therapeutic vaccines are currently in various stages of development. The goal is to develop a preventative vaccine that can protect people from HIV infection, or at least reduce the chances of being infected with HIV following exposure to the virus. Therapeutic HIV vaccines are designed to control HIV infection in people who are already infected with HIV and as such are potentially one arm of a cure strategy. While vaccines developed for prevention are being tested in therapeutic modalities, these studies are in very early stages of research.

Can you give an overview of the vaccines that have advanced to efficacy testing in humans?

One vaccine to enter Phase II trials was an adenovirus-based vaccine developed by Merck & Co. Unfortunately this vaccine was a failure and the trial was stopped. The Thai Phase III HIV vaccine trial, otherwise known as the RV144 trial, showed more positive results, exhibiting a moderate efficacy. A number of studies are planned to follow-up on the efficacy of this vaccine. There is currently only one other vaccine in efficacy trials and that is the vaccine developed by the NIH. This is a prime-boost strategy which uses a DNA plasmid vaccine for the prime (initial) vaccination followed by a recombinant adenoviral vector vaccine, the booster vaccination. This vaccine stimulates antibodies and killer T cells. It’s currently in Phase IIb testing and we expect results in 2014.

Can you explain what broadly neutralising antibodies are and their implications for vaccine development?

We’ve been studying individuals that have had long-term HIV infection and have isolated antibodies that neutralise a broad range of HIV strains. We hope to make a vaccine that could stimulate the human immune system to make similar antibodies. The discovery of these antibodies will hopefully lead to new vaccine strategies. During the last three years there has been an explosion in the identification of broadly neutralising antibodies. We are currently designing components of a candidate vaccine and this is still at a very early stage of development. An effective vaccine based on this strategy may require giving multiple shots and long-term exposure to obtain optimal efficacy.

What is your vision on the most likely way forward with HIV vaccine development? What would you put your money on?

I believe that we need to develop new HIV envelope antigens in the research laboratory and that we need to develop a step-wise approach for predicting how these antigens can be used to direct the immune response to generate broadly neutralising antibodies. While this is very a very complicated strategy, I believe that a vaccine based on this new approach may deliver the best results.

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