Professor of Vaccine Immunology, MSc BSc PhD
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.
Antiretroviral therapy alone versus antiretroviral therapy with a kick and kill approach, on measures of the HIV reservoir in participants with recent HIV infection (the RIVER trial): a phase 2, randomised trial.
Fidler S. et al, (2020), Lancet (London, England), 395, 888 - 898
Novel Nested Peptide Epitopes Recognized by CD4+ T Cells Induced by HIV-1 Conserved-Region Vaccines.
Borthwick N. et al, (2020), Vaccines, 8
Corrigendum to 'Therapeutic vaccination refocuses T-cell responses towards conserved regions of HIV-1 in early treated individuals (BCN 01 study)' EClinicalMedicine 11 (2019) 65-80.
Mothe B. et al, (2020), EClinicalMedicine, 18
HIVconsv Vaccines and Romidepsin in Early-Treated HIV-1-Infected Individuals: Safety, Immunogenicity and Effect on the Viral Reservoir (Study BCN02).
Mothe B. et al, (2020), Frontiers in Immunology, 11
In vivo Effects of Romidepsin on T-Cell Activation, Apoptosis and Function in the BCN02 HIV-1 Kick&Kill Clinical Trial.
Rosás-Umbert M. et al, (2020), Frontiers in immunology, 11