Prof Quentin Sattentau
	Tel:	+44 1865 275 511
	E-mail:	quentin.sattentau@path.ox.ac.uk
	Address:	Sir William Dunn School of Pathology, University of Oxford South Parks Road, Oxford OX2 0AU
	Website:	http://users.path.ox.ac.uk/~qsattentau/index.htm

Principal areas of research
Cell biology of HIV assembly, exit and cell-cell spread, HIV neutralising antibody vaccine design and development, retrovirus entry inhibitors, mechanisms and applications, reactive carbonyls in allergy and hypersensitivity.

Biography
Obtained a BSc (Hons) degree in Microbiology from the University of Bristol, UK in 1980, and a PhD in immuno-virology from the London Hospital Medical School, University of London, in 1985. He carried out postdoctoral research with Dr Peter Beverly at The Imperial Cancer Research Fund Laboratories, Middlesex Hospital and University College Medical School, University of London, and became Research Lecturer in 1997. From 1988-2000 he was an MRC visiting Scientist in the laboratory of Dr. Richard Axel, Columbia University, NY, USA. In 1991 he joined the Centre d’Immunologie de Marseille-Luminy in Marseille, France, as a tenured CNRS scientist, grade Director of Research level 2 (DR2). In 1998 he returned to the UK and spent a year as a visiting scientist in the Sir William Dunn School of Pathology, University of Oxford. He subsequently worked as Senior Lecturer, then Reader, in the Jefferiss Trust Research Laboratories, Imperial College London. In 2003 he joined the faculty at the Dunn School of Pathology, and Magdalen College, University of Oxford, as Lecturer and Tutorial Fellow in Molecular Microbiology, was awarded the title of Reader in Immunology in 2004, and the title of Professor in Immunology in 2006. His research team, based in the Dunn School of Pathology, is focussed primarily on research into HIV pathogenesis and antibody-based HIV vaccine design.

Research
Despite intense activity by the international research community, we do not have an effective vaccine against HIV-1 infection. Neutralising antibodies are an important component of the anti-HIV immune response and a protective prophylactic vaccine will need to elicit such antibodies. We have a growing understanding of the antigenicity of the target of HIV-specific neutralising antibodies, the viral glycoproteins, Env. Nevertheless, no laboratory has yet induced the requisite high levels of neutralising antibodies following immunisation and the problem appears to be due to an unfocussed antibody response and the innately poor immunogenicity of HIV Env. We are attempting to focus the antibody response to the relevant epitopes by a strategy of ‘immune silencing’ of irrelevant epitopes that has been developed by our group. Moreover, we are attempting to improve the immunogenicity of Env by developing novel adjuvants and by harnessing elements of the innate immune response including glycan recognition and Toll Like Receptor (TLR) activation.

One factor limiting progress in vaccine antigen design is our limited knowledge of the structure of the viral spike, the target of neutralizing antibodies. Our extensive collaboration with Stephen Fuller at the Wellcome Trust Structural Biology Centre, University of Oxford, has allowed us to investigate the structure of the SIV spike in situ on the virion particle. This has revealed information relating to Env structure and function, with particular relevance to antibody immune evasion by HIV-1. Future studies are aimed at elucidating the HIV-1 spike structure, both in its unligated form, and engaged by ligands such as neutralising antibodies and receptor mimics.

Since HIV is primarily transmitted via the mucosae, it will be important for antiviral antibodies induced by vaccination to be functional at these surfaces. In the context of the Grand Challenges in Global Health, established by the Bill and Melinda Gates Foundation, we are developing a mucosal immunisation system in which vaginal microbicides will be combined with HIV-1 Env antigen for vaginal immunisation. The microbicide-antigen formulation would be expected to induce local mucosal immunity in the form of neutralising IgA and IgG antibodies, that would add to the barrier against incoming virus. If successful, this strategy would be the first self-applied, mucosally-active vaccine. We have established in vivo models of vaginal immunisation, and have demonstrated successful induction of Env-specific mucosal IgA and IgG. These preclinical studies are informing associated clinical trials due to start this year. The successful development of an HIV vaccine will in part depend on a better understanding of viral pathogenesis, and particularly of virus dissemination between permissive cells in the infected host.

Viruses use two mechanisms to spread within a host: release of cell-free particles and direct, cell-to-cell spread. Cell-cell spread of HIV may confer advantages over cell-free spread, such as more rapid viral replication and dissemination, and resistance to elements of the humoral immune response. We have established in vitro systems to investigate cell-cell spread of HIV-1. Upon contact with receptor-bearing cells, HIV-1-infected T cells induce the formation of a “virological synapse” in which viral receptors and adhesion molecules rapidly co-cluster with viral envelope glycoproteins. We were the first group to demonstrate such an HIV-1-induced structure in T cells and are currently characterising the molecular associations underlying the formation of the synapse and its role in viral spread and pathogenesis. We are analysing T cells from individuals with genetically-defined defects in the secretory pathway to dissect the molecular steps in viral assembly and exit. Parallel studies are aimed at inhibiting this mode of viral dissemination by neutralising antibodies.

Key Publications
Jolly C and Sattentau QJ. (2007). HIV-1 assembly, budding and cell-cell spread in T cells takes place in tetraspanin-enriched plasma membrane. J. Virol. May 23 Epub ahead of print.

Jolly C, Mitar I and Sattentau QJ (2007). Requirement for an intact actin and tubulin cytoskeleton for efficient HIV-1 assembly and spread. J. Virol. March 14 Epub ahead of print.

Sheppard NC, Bates AC and Sattentau QJ (2007). A functional human IgM response to HIV-1 Env after immunization with NYVAC-HIV C. AIDS 21: 524-527

Zanetti G, Briggs JAG, Grunewald K, Sattentau QJ* and Fuller SD* *Joint corresponding authors. (2006). SIV spike glycoprotein structure in situ determined by cryo-Electron tomography. Plos Pathogens 2:e83

Moghaddam A, Olszewska W, Wang B, Tregoning JS, Helson R, Sattentau QJ* and Openshaw PJM* *Joint senior authors (2006). A potential molecular mechanism for hypersensitivity caused by formalin-inactivated vaccines. Nature Medicine 12: 905-907.

Zhou, T, Hamer, D, Hendrickson, WA, Sattentau, QJ and Kwong, PD. (2005). Interfacial metal and antibody recognition. PNAS USA 102:14575-80.

Jolly C and Sattentau QJ. (2005). Human Immunodeficiency virus type-1 virological synapse formation in T cells requires lipid raft integrity. J. Virol. 79: 12088-12094.

Piguet, V and Sattentau, QJ. (2004). Dangerous Liasons at the Virological Synapse. J. Clin. Invest. 114: 2-8.

Jolly, C, Kashefi, K, Hollinshead, M and Sattentau, QJ. (2004). HIV-1 cell-to-cell transfer across an Env-induced, actin-dependent synapse. J. Exp Med. 199: 283-193.

Klasse PJ, Sattentau QJ (2002). Occupancy and mechanism in antibody-mediated neutralization of animal viruses. J Gen Virol. 83:2091-108.

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