Principal areas of research
Analysis of innate and T cell responses in acute HIV-1 infection; identification of innate correlates of resistance to HIV infection; characterisation of innate responses in acute and chronic hepatitis C infection. Overall objective – to inform HIV (and HCV) vaccine design via identification of correlates of immune protection.

Biography
Dr Borrow obtained a BA (Hons) degree in Natural Sciences from the University of Cambridge, UK in 1985, and a PhD degree, also from the University of Cambridge, UK, in 1989. She then carried out postdoctoral research with Dr Michael Oldstone at The Scripps Research Institute, La Jolla, USA, becoming a Senior Research Associate (Instructor) in 1992 and an Assistant Member (Assistant Professor) at The Scripps Research Institute in 1995. In 1997, she moved back to the UK to become a Group Leader at the newly-established Edward Jenner Institute for Vaccine Research, where she was promoted to the position of Senior Group Leader in 2003. In 2005 she joined the Nuffield Department of Clinical Medicine at the University of Oxford as a Senior Jenner Fellow. Her research team, based in the Jenner building in Compton, is carrying out basic research aiming to inform vaccine design.

Research
There is an urgent need for vaccines to combat infection with human immunodeficiency virus type 1 (HIV-1), persistent infection with which is associated with development of an acquired immunodeficiency syndrome (AIDS) currently responsible for ~3 million deaths per year worldwide. A key goal of prophylactic HIV vaccine strategies is to induce rapidly-acting immune responses able to modulate the events in early infection that are now known to be critical determinants of the subsequent disease course: establishment, local expansion and dissemination of infection, exponential acute viral replication (resulting in depletion of the memory CD4+ T cell pool), followed by partial containment of viral replication and establishment of a setpoint persisting viral load. Definition of the component(s) of an immune response able to intervene and mediate protection at this time would remove one of the major roadblocks currently hampering rational HIV vaccine design.

Innate responses can be activated very rapidly in response to pathogen exposure or infection, and play important roles both in containment of early pathogen replication and promotion of induction of the adaptive response. We thus hypothesise that the nature of the innate response in acute HIV-1 infection and its interaction with the adaptive response may be among the factors involved in determining the prognostically important setpoint viral load and central memory CD4+ T cell level; and that innate responses may contribute to the resistance exhibited by certain individuals to full, seropositive HIV infection despite repeated viral exposure (the exposed uninfected (EU) phenotype). A key implication of this is that innate responses could be harnessed to form an important component of vaccine-elicited protective immunity, where rapid triggering of effector functions on exposure to HIV or HIV-infected cells is likely to be critical. One series of projects ongoing within the group are addressing these hypotheses. We are also carrying out some comparative analysis of innate responses in acute and chronic hepatitis C virus infection.

T cell responses play a key role in the elimination of many established virus infections, and multiple lines of evidence suggest that HIV-specific CD8+ T cells play an important role in both the initial containment of primary viraemia and subsequent control of ongoing viral replication. Prophylactic and therapeutic strategies to combat HIV infection are thus being designed to invoke this arm of the immune response. However the primary HIV-specific CD8 T cell response remains relatively poorly characterised, and how aspects of this response and its subsequent maintenance or evolution may impact on the initial and longer-term efficiency of control of virus replication are not well understood. A second series of projects within the group are analysing the relationship between qualitative aspects of the virus-specific CD8+ T cell response induced in primary HIV infection, the extent and kinetics of viral mutational escape from CD8+ T cell control, and the subsequent efficiency of control of viral replication.

Key Publications
Turnbull, E.L., A.R. Lopes, N.A. Jones, D. Cornforth, P. Newton, D. Aldam, P. Pellegrino, J. Turner, I. Williams, C.M. Wilson, P.A. Goepfert, M.K. Maini, and P. Borrow. HIV-1 epitope-specific CD8+ T cell responses strongly associated with delayed disease progression cross-recognize epitope variants efficiently. J. Immunol. 176:6130-6146, 2006.

Meier, U.-C., R.E. Owen, E. Taylor, N. Naoumov, C. Willberg, K. Tang, D. Cornforth, P. Newton, P. Pellegrino, I. Williams, P. Klenerman and P. Borrow. Shared alterations in NK cell frequency, phenotype and function in chronic human immunodeficiency virus and hepatitis C virus infections. J. Virol. 79:12365-12374, 2005.

Montoya, M., M.J. Edwards. D.M. Reid and P. Borrow. Rapid functional activation of spleen dendritic cell subsets following lymphocytic choriomeningitis virus infection of mice: involvement of type I interferon. J. Immunol. 174: 1851-1861, 2005.

Jones, N.A., X. Wei, D.R. Flower, M. Wong, F. Michor, M.S. Saag, B.H. Hahn, M.A. Nowak, G.M. Shaw and P. Borrow. Determinants of HIV-1 escape from the primary CD8+ cytotoxic T lymphocyte response. J. Exp. Med. 200: 1243-1256, 2004.

Gloster, S.E., P. Newton, D. Cornforth, J.D. Lifson, I. Williams, G.M. Shaw and P. Borrow. Association of strong virus-specific CD4+ T cell responses with efficient natural control of primary HIV-1 infection. AIDS 18: 749-55, 2004.

LeBon, A., N. Etchart, C. Rossman, M.J. Ashton, S. Hou, D. Gewert, P. Borrow and D.F. Tough. Cross-priming of CD8+ T cells stimulated by virus-induced type I interferon. Nature Immunol. 4: 1009-1015, 2003.

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