World AIDS Day 2016: An Oxford-Japan Collaboration

Every year World AIDS Day is marked on 1^st December.  Across NDM, research is being carried out into HIV/AIDS to understand more about the disease and to ultimately find a prevention and cure. NDM spoke to Tomáš Hanke, Professor of Vaccine Immunology, University of Oxford and Distinguished Professor, Kumamoto University about his ongoing collaborative research to develop an HIV vaccine.

Q: What are the challenges in developing a vaccine for HIV?

Tomáš Hanke: The biggest roadblock for HIV-1 vaccines is the huge HIV variability and its ability to evade the immune response. Every time the body launches an immune response as a result of HIV infection, HIV changes its coat and becomes invisible to the immune system and escapes. However, even HIV may have its Achilles heel - the functionally conserved regions of virus proteins that cannot vary without reducing HIV’s ability to replicate and infect new cells. Most global HIV-1 strains share these conserved proteins and we have designed a vaccine to target them.

Q: What are CD8 T cells and why might this immune response be important for developing an HIV vaccine?

TH: We aim to develop a vaccine that can induce an immune response involving a particular type of T cells - so called killer CD8 T cells. These T cells target and destroy HIV-infected cells. Virus-specific CD8 T-cell responses are induced throughout HIV-1 infection and there is a growing evidence that their specificity is critical for protection against HIV-1. Therefore, vaccine-induced CD8 T cells should target HIV conserved regions, both to match as many circulating HIV-1 variants as possible and also to prevent virus escape during infection. I and Andrew McMichael have spent many years thinking about and developing HIV-1 vaccines that will induce effective CD8 T-cell responses. In collaboration with Bette Korber from the Los Alamos National Laboratory, we have designed our vaccines as mosaic proteins, which are computed using all the over 5000 HIV sequences in the database to maximized the match to global HIV-1 variants.

Q: Can you tell us more about your collaboration in Japan?

TH: We pioneered testing the first conserved region vaccine in both HIV-negative and HIV-positive adults. These initial studies proven the concept that conserved regions can induce strong CD8 T-cell responses when delivered by potent and well-trialled prime-boost approach used in several candidate vaccines under development in the Jenner Institute.

I have taken advantage of my part-time appointment at Kumamoto University and generated with my Japanese colleagues supporting data for our conserved mosaic design. We have tested the recognition of the vaccine-derived peptides in treatment-naïve Japanese patients and found that patients with stronger and broader CD8 T-cell responses to the vaccine peptides had significantly lower viral load and higher CD4 T-cell counts, that is control the virus better and are healthier. Furthermore, we found evidence that our strategy may protect not only the lucky individuals with the right tissue types, but may be effective in the general population.

While our vaccine design has a strong theoretical rationale, we shall only find out if our strategy works if it helps high-risk individuals from getting infected, or holds the virus replication down after stopping antiretroviral treatment in infected patients. These studies are now on the horizon!

The work is supported by Medical Research Council UK, European AIDS Vaccine Initiative 2020, National Institutes of Health and the International AIDS Vaccine Initiative.