Professor of Vaccine Immunology, Distinguished Professor, Kumamoto University
Professor Tomas Hanke's research aims to develop a universal HIV-1 vaccine, which targets most global virus variants including escape mutants. He strives to maintain a balance between basic and translational research. He oversees a busy pre-clinical programme encompassing HIV-1 epitope discovery and dynamics using mass spectrometry and T-cell assays, studies on immunodominance, depth (number of variants) of epitope recognition and the importance of perfect vaccine-virus epitope matching for effective effector functions. He explores novel vaccine modalities and optimize their immunogenicity in heterelogous prime-boost regimens in mice and macaques. He co-ordinates a clinical programme assessing candidate HIV vaccines in humans in UK, Europe and Africa.
The biggest challenges for vaccine development are HIV-1 diversity and escape. To tackle these, we have developed T-cell immunogen HIVconsv, which directs vaccine-induced responses to the most functionally conserved regions of the HIV-1 proteome and thus targets both diverse clades circulating in the population and escape mutants generated in infected individuals. Because these regions are functionally conserved, HIV-1 cannot easily change and escape them without a significant cost to its replicative fitness. The HIVconsv vaccines have entered 8 clinical trials and showed high immunogenicity in HIV-negative adults in Oxford and Kenya as well as in HIV-infected patients on antiretroviral treatment.
A second generation conserved mosaic vaccines called tHIVconsvX has been developed with significantly improved coverage of global HIV-1 variants and delivery. These are being characterised in pre-clinical models and are in the pipeline for clinical trials. The tHIVconsvX-induced T-cells will complement Ab vaccines while the induction of broadly neutralising antibodies remains suboptimal and will likely be key for HIV cure.
In collaborations, we are assessing the importance of vector priming on induction of broadly neutralizing antibodies against HIV-1. Co-delivery of antibody and T-cell vaccines will optimised.
The laboratory aims to stay one step ahead of the clinical testing, developing improved next generation immunogens, vectors and regimens.