Dr Tomáš Hanke
	Tel:	+44 (0)1865 222 355
	E-mail:	tomas.hanke@imm.ox.ac.uk
	Address:	Weatherall Institute of Molecular Medicine, University of Oxford The John Radcliffe Hospital, Oxford OX3 9DS
	Website:	www.imm.ox.ac.uk/pages/research/human_immunology/tomas_hanke.htm www.jenner.ac.uk/vaccine_prog_hiv.html

Principal areas of research
Development of HIV-1 vaccine inducing protective T cell responses.

Biography
Dr. 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 main hypothesis my laboratory aims to test is that high frequency and/or quality of vaccine-induced HIV-1-specific T cells, in the absence of viral envelope-specific antibody, can substantially improve resistance to HIV-1 infection.

For a number of years, we have been developing an HIV-1 vaccine focusing on induction of protective cell-mediated responses. Our starting platform was based on a heterologous DNA prime and recombinant modified vaccinia virus Ankara (rMVA) boost regimen delivering a common immunogen called HIVA, which is derived from consensus HIV-1 clade A Gag protein, i.e. an immunogen derived from an HIV-1 strain prevalent in Central and Eastern Africa, and a string of CD8+ T cell epitopes Extensive complementing studies in mice, non-human primates (NHP) and over four hundred healthy and HIV-1-infected humans showed that the vaccines are safe and immunogenic. In humans, the pTHr.HIVA DNA vaccine primed weakly, but consistently HIV-1-specific mostly CD4+ T cell responses, and the MVA.HIVA vaccine delivered a strong and consistent boost expanding both CD4+ and CD8+ HIV-1-specific T cells if these are well primed, e.g. by HIV-1 infection. Therefore, needle-injected DNA is likely to be a limiting factor for the vigor of the DNA prime-rMVA boost-induced response and we shall evaluate other priming strategies in humans that show greater promise in pre-clinical studies.

HIVA has proven extremely useful as a model immunogen for both pre-clinical and clinical comparative studies of a number of vaccine vectors and vaccination regimens. The modalities we use in the laboratory include Semliki Forest virus, human and animal adenoviruses and Bluetongue virus-derived tubules. All these constructs infect human cells and/or deliver directly or through cross-priming HIV-1-derived peptides into the MHC class I presentation, but replicate poorly or not at all.

Most recently, a recombinant Mycobacterium bovis bacillus Calmette-Guérin (BCG) expressing HIVA was generated and shown to be stable and induce durable high-quality HIV-1-specific CD4+ and CD8+ T cell responses. Furthermore, when used in a heterologous prime-boost regimen, protection against surrogate virus challenge through the HIV-1-specific responses were achieved and BCG.HIVA alone protected against aerosol challenge with M. tuberculosis. Thus, this promising approach provides a platform for development of a dual HIV-1/tuberculosis vaccine for breastfed infants born to HIV-1-positve mothers.

We construct novel HIV-1-derived vaccine immunogens. To broaden immune responses induced by HIVA, we designed a second complementing immunogen, called RENTA, which consists of inactivated reverse transcriptase, inactivated tat and parts of nef and gp41, all derived from the consensus HIV-1 clade A sequence. Initially, we shall use this second immunogen together with HIVA in therapeutic clinical trials in Oxford. Also, an immunogen based on conserved regions of the HIV-1 proteome has been constructed and evaluated using mice and PBMC from HIV-1-infected patients.

In summary, the laboratory develops novel vaccine modalities and evaluates them in various heterologous prime-boost strategies not only for the peak frequency, but also for the quality, location and longevity of vaccine-induced T cells in mice and NHP. The most promising approaches are tested in rapid, small, highly informative phase I clinical trials designed to optimize vaccine dose and delivery in humans and to provide a feedback for the pre-clinical vaccine improvements.

Key Publications
Im E-J, Saubi N, Virgili G, Sander C, Teoh D, McShane H, Joseph J and Hanke T. Vaccine platform for prevention of tuberculosis and mother-to-child transmission of HIV-1 through breastfeeding. J Virol 81:9408-9418 (2007).

Im E-J and Hanke T. Pre-clinical evaluation of candidate HIV type1 vaccines in inbred strains and an outbred stock of mice. AIDS Res Hum Retroviruses 23: 857-862 (2007).

Hanke T, McMichael AJ, and Dorrell L. Clinical experience with plasmid DNA- and modified vaccinia virus Ankara (MVA)-vectored HIV-1 clade A vaccine focusing on T cell induction. J Gen Virol 88: 1-12 (2007).

Larke N, Im E-J, Wagner R, Williamson C, Williamson A-N, McMichael AJ and Hanke T. Combined single-clade candidate HIV-1 vaccines induces T cell responses limited by multiple forms of in vivo immune interference. Eur J Immunol 37: 566-577 (2007).

Im E-J, Nkolola JP, di Gleria, McMichael AJ and Hanke T. Induction of long-lasting multi-specific CD8+ T cells by a 4-component DNA-MVA/HIVA-RENTA candidate HIV-1 vaccine in rhesus macaques. Eur J Immunol 36:2574-2584 (2006).

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)

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