Theme 1: From bench to bedside (and back)

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Overview

Overview

From bench to bedside (and back) research is centered largely on clinical trials that can be performed in our dedicated clinical area within CII Q block, many conducted through the joint ventures with York Hospital and in association with the Vaccine Institute, St George's London.

Funded by the Bill and Melinda Gates Foundation, the Wellcome Trust, the European Commission and the NIH, we conduct phase 1 trials of mucosal vaccines and microbicides against HIV-1 (Phase I trial to start in 2014), with a focus on finding safe, effective and easily accessible interventions for women in developing countries. 

Other genital tract infections investigated in human volunteers include Chlamydia and HPV (HPV vaccine trial started in 2014). 

A first-in-man trial of a new therapeutic vaccine for visceral leishmaniasis started in 2013, funded by a Wellcome Trust Translation Award.

Projects

Projects

From bench to bedside (and back) research

The year 2011 marks 30 years of AIDS. In that time, AIDS has claimed more than 25 million lives and more than 60 million people have become infected with HIV. Still, each day, more than 7,000 people are newly infected with the virus, including 1,000 children. No country has escaped the devastation of this truly global epidemic. Nevertheless, HIV programmes are now bearing fruit, with global HIV incidence declining, treatment access expanding and an unparalleled global movement mobilized to demand respect for the dignity and human rights of everyone vulnerable to, and affected by, HIV. The next stage in control of this global pandemic is to continue to strive towards the elimination of new infections.

Professor Charles Lacey's group conducts phase 1 clinical trials of vaccines and microbicides against HIV-1. The group has collaborators worldwide and is funded by awards from the Bill and Melinda Gates Foundation, the Wellcome Trust, and the European Commission. The focus of the group is directed towards finding safe, effective and easily accessible preventative interventions against HIV-1 for women in developing countries. We have just completed two phase 1 trials: a novel HIV vaginal vaccine utilising CN54gp140, in conjunction with the Vaccine Institute, St George's, University of London, as part of a Gates Grand Challenges award; and a microbicide trial (MABGEL1) of monoclonal anti-HIV antibodies C2F5, C2G12 and C4E10, both in vaginal gel formulations. We are also taking part in a multicentre trial examining the efficacy of switching to boosted protease inhibitor monotherapy versus continuing combination antiretroviral therapy for the long-term management of HIV-1 infected patients (PIVOT trial). A substudy examining whether this antiviral therapy suppresses viral load in the genital and rectal tracts in these patients, is being led by the Lacey group.

The group has a number of other projects investigating genital tract immunology, including aspects of Chlamydia immunopathogenesis and genetic diversity. Internal collaborations include the development of therapeutic CD8+ T cell-biased vaccines for visceral leishmaniasis with the Kaye groups in the CII, and investigations to determine whether an IgG transporter system, FcRn, is expressed and functional in the female genital tract.

Links:

Europrise - microbiocides and vaccines

Mucosal HIV Vaccine Project (MUCOVAC)

European Microbiocides Project (EMPRO)

Combined Highly Active Anti-Retroviral Microbiocides project (CHAARM)


Leishmaniasis

Leishmaniasis affects approximately 15m people in 88 countries, results in approximately 100,000 deaths annually, and has a significant impact on health in developing countries. In southern Europe and countries bordering the Mediterranean, leishmaniasis is a major opportunist infection in HIV-infected individuals. Research on leishmaniasis in the Centre is wide ranging and multidisciplinary, including molecular, biochemical and immunological studies.

Research on the immunology of leishmaniasis focuses on disease caused following infection with visceralising species of Leishmania (L. donovani and L. infantum), though comparative research using parasites that cause other forms of disease (cutaneous, mucocutaneous) are also conducted. We have developed novel transgenic lines of Leishmania, that express fluorescent or biophotonic (luciferase) reporter genes and / or defined reporter antigens. These parasites allow us to monitor disease progression non-invasively and by stereo-, confocal and 2-photon microscopy, and to monitor host T cell responses and antigen presenting cell function using TCR transgenic model systems. A major area of research interest is in understanding how immune-mediated pathology contributes to immune-suppression associated with visceral leishmaniasis. Capitalising on the availability of comparative genome sequence data for the major species of Leishmania, we are generating targeted mutant lines to identify survival and virulence factors. Our immunological research into visceral leishmaniasis is funded by Programme Grants from the MRC and the Wellcome Trust. Our vaccine research programme is focused on the development of therapeutic CD8+ T cell-biased vaccines for visceral leishmnaiasis. Funding to develop this work to a first-in- man study in UK volunteers has recently been awarded by the Wellcome Trust.

Featured publication

Pre-exposure prophylaxis to prevent the acquisition of HIV-1 infection (PROUD): effectiveness results from the pilot phase of a pragmatic open-label randomised trial Sheena McCormack*, David T Dunn*, Monica Desai, David I Dolling, Mitzy Gafos, Richard Gilson, Ann K Sullivan, Amanda Clarke, Iain Reeves, Gabriel Schembri, Nicola Mackie, Christine Bowman, Charles J Lacey, Vanessa Apea, Michael Brady, Julie Fox, Stephen Taylor, Simone Antonucci, Saye H Khoo, James Rooney, Anthony Nardone, Martin Fisher, Alan McOwan, Andrew N Phillips, Anne M Johnson, Brian Gazzard, Owen N Gill. Lancet 2015 Sep 9.

Research at CII