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.
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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.
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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.
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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.
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The laboratory aims to stay one step ahead of the clinical testing, developing improved next generation immunogens, vectors and regimens.
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