The long term aim for Professor Tomáš Hanke is to develop a safe, effective and accessible HIV-1 vaccine. His group tests novel ideas and vaccine strategies, and focusses on a safe but rapid translation of the most promising laboratory results to phase I/II clinical trials in human volunteers.
Big challenges face the development of an HIV vaccine, including the enormous HIV variation. Professor Hanke focusses on the most conserved regions of the HIV-1 proteome, and also works on the development of a vaccine both for adults and against mother-to-child transmission. The ultimate goal is to create an effective universal HIV vaccine.
Ultimately, medical research must translate into improved treatments for patients. At the Nuffield Department of Medicine, our researchers collaborate to develop better health care, improved quality of life, and enhanced preventative measures for all patients. Our findings in the laboratory are translated into changes in clinical practice, from bench to bedside.
Q: HIV shows huge antigenic variation. How can we develop a vaccine?
TH: That is correct. The biggest challenge in the development of an effective HIV vaccine is the enormous HIV variation, which means that HIV has an enormous capacity to change. That is, every time the body launches an immune response as a result of HIV infection of after vaccination, HIV changes its coat and becomes invisible to this immune response and escapes. Fortunately, there is a limit to HIV variation and even HIV cannot change completely and has to keep small parts of its proteins conserved so that it survives and it is this Achilles heel of HIV that we are focusing on with our vaccines. This comes with another advantage; on different continents or different geographic regions HIV evolved into different Subtypes but, again, all these Subtypes have to have these conserved regions in common. Therefore if our vaccine works it can be deployed in Africa, Asia, Europe, America – it would be universal. Finally, the strength of our vaccine approach also comes from using a unique and very potent combination of different vaccine Subtypes which together induce very strong immune responses.
Q: How can we stop the transmission from mothers to their babies?
TH: Most, but not all, HIV transmission from HIV infected mothers to babies can be prevented by antiretroviral drugs. However, in developing countries, these drugs are not readily available and their use is associated with harmful unwanted side effects and also there is a possibility that HIV again changes and becomes, in this case, resistant to HIV drugs. Therefore, as a result, unacceptably high numbers of babies become infected through breast feeding. Just like for the whole HIV epidemic, the best solution for protecting babies against HIV is the development of a safe and effective HIV vaccine given to adults to decrease the number of HIV-infected mothers, and given to babies at birth to protect them against their mother's virus in the breast milk. Just like for the adult vaccine, we are developing a pediatric vaccine which focuses on the conserved regions of HIV.
Q: Can your research help us to design other vaccines?
TH: There are many difficult infections and diseases like cancer which can use exactly the same tools to induce strong and protective immune responses. And just like we are learning from other groups' approaches and innovations, other groups can learn from us.
Q: What are the most important lines of research that have developed over the past five or ten years?
TH: Many new exciting molecular tools and technologies have become available which on the one hand allow us to induce more potent and vigorous immune responses, and on the other hand allow us to measure them and characterise them in much more greater detail. As for HIV vaccines, after the first two failures of candidate HIV vaccines, the third vaccine in so called Thai trial induced marginal protection. This was an enormous boost to the whole HIV vaccine development field. Of course, this observation has to be reproduced.
Q: Why does your line of research matter – why should we put money into it?
TH: HIV infection and AIDS remain one of the most pressing global health problems and development of a safe effective accessible preventive HIV vaccine is the best and cheapest solution.
Q: How does your research fit into translation medicine within the department?
TH: Developing vaccines is an excellent example of translational medicine – while testing our ideas for vaccines in models is important and saves lots of money and time, at the end of the day what matters is what happens in humans. Our group tests lots of ideas in the laboratory, but focuses on safe and rapid translation of the most promising observations into humans. Therefore, our programme fits very well with the translation activities of the department.