Prof Tomas Hanke
| Address: | The Jenner Institute, Old Road Campus Research Building |
| Tel: | +44 (0)1865 617630 |
| Email: | |
| Website: | HIV Vaccine Programme |
Principal areas of research HIV-1 vaccines |
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Biography
Prof Hanke started his undergraduate studies at Charles University in Prague, Czech Republic reading Chemistry and completed his B.Sc. Honours degree in Biochemistry at McMaster University in Hamilton, Canada, where he also received an M.Sc. for his studies on Herpes simplex virus immunology. He then moved to St. Andrews University in Scotland for his Ph.D. degree developing antiviral-vaccines as solid matrix-antibody-antigen complexes.
In 1994, he arrived as a post-doctoral scientist in Professor McMichael’s laboratory in the Weatherall Institute of Molecular Medicine in Oxford, where he started working on the development of HIV vaccines, his current interest. With the establishment of the MRC Human Immunology Unit in 1998, he started his own group and 5 years later, he obtained his MRC tenure position. Since 2003 and 2007, he has been a University of Oxford Research Lecturer and a Jenner Institute Investigator, respectively.
Research
The long-term objective of my laboratory is to develop an effective HIV-1 vaccine. We concentrate on induction of cell-mediated immunity, and combine novel approaches and newly emerging technologies to maximize the potential for inducing protective T cell responses. In essence, we design new vaccines and progress them in an iterative process from bench construction to first mouse, then to non-human primate and finally to human testing; results from all stages feed back to the basic vaccine improvements.
We hypothesized that focusing early vaccine-induced T cell responses against conserved regions of HIV 1 will lead to a better recognition of infecting viruses and better control of escaping viruses.
HIV-1 has an enormous capacity to change. Some HIV-1 proteins such as the envelope are more variable than e.g. the internal structural proteins. On a sub-molecular level, some protein regions have to remain more-or-less constant to maintain their structural or biological functions and, therefore, even HIV-1 has its Achilles heel and this can be exploited. Focusing the vaccine-elicited responses on the functionally conserved regions of the HIV-1 proteome has a number of advantages. Firstly, conserved regions are common to the diverse virus strains and clades to which vaccinees are exposed. Secondly, targeting the conserved regions reduces the chance of virus escape in infected individuals. If escape mutations do occur, and some have been documented in conserved regions, they may often decrease virus fitness or may require compensating mutation(s). Therefore, escape mutations in the conserved regions may be good for the patient’s clinical prognosis or may be very delayed. Thirdly, T-cell immunogens based on the functionally conserved parts of HIV-1 proteins redirect the naturally induced hierarchy of epitope responses, which is non-protective, towards invariable regions, which are arguably more likely to be protective.
Finally, conserved immunogens can be designed as a simple single insert, representative of the major global clades A, B, C and D equally. Therefore, vaccines based on the conserved regions of the HIV-1 proteome can be tested and potentially deployed in Europe, America, Asia and Africa; they are universal. The first conserved region vaccine entered clinical evaluation in HIV-1 seronegative volunteers in Oxford, UK and the results are expected in summer 2012.
Key Publications
Rosario M, Borthwick N, Stewart-Jones GB, Mbewe-Mvula A, Bridgeman A, Colloca S, Monefiori D, McMichael AJ, Nicosia A, Drijfhout JW, Melief CJ, and Hanke T. Prime-boost regimens with adjuvanted synthetic long peptides elicit T cells and antibodies to conserved regions of HIV in macaques. AIDS In press (2012).
Hanke T, and McMichael AJ. HIV-1: From escapism to conservatism. Eur J Immunol In press (2011).
Im E-J, Hong JP, Roshorm Y, Bridgeman A, Létourneau S, Liljestrom P, Potash MJ, Volsky DJ, McMichael AJ and Hanke T. Protective efficacy of serially up-ranked subdominant CD8+ T cell epitopes against virus challenge. PLoS Pathog 7: e1002041 (2011).
Létourneau S, Im E-J, Mashishi T, Brereton C, Bridgeman A, Yang H, Dorrell L, Dong T, Korber B, McMichael AJ and Hanke T. Design and pre-clinical evaluation of a universal HIV-1 vaccine. PLoS ONE 2:e984 (2007).
Hanke T, and McMichael AJ. Design and construction of an experimental HIV-1 vaccine for a year-2000 clinical trial in Kenya. Nat Med 6, 951-955 (2000).
