Microbicides 2004 Microbicides 200428-31 March 2004, Hilton London MetropoleThe conference42 million men, women and children worldwide were living with HIV by the end of December 2002 (source: UNAIDS), including five million newly-infected during that year alone. Another 45 million people will become infected between 2002 and 2010, unless the current transmission rates can be vastly reduced. Of the 42 million, 29.4 million live in sub-Saharan Africa and 58% of them are women. Not only are women more susceptible to HIV infection, many are powerless to insist on the use of condoms or other methods of protecting themselves. In this context, and with the knowledge that an effective HIV vaccine is unlikely to be available for several years, the need for an effective topical microbicide grows ever more urgent. 2004 should prove to be a landmark year in the field of microbicide development as the first Phase III trials of novel products are due to start – the next step along the road to making a microbicide available to the millions worldwide in desperate need of protection.The aims of the Microbicides 2004 conference are to:Report novel or innovative work in the microbicides fieldProvide updates on recent microbicides research, divided into three tracks: basic science, clinical science, and behavioural science (including public health and the microbicide marketplace)Provide a forum for the discussion of new developments in microbicide research including ethical, clinical, behavioural and methodological issuesPresent opportunities for knowledge-sharing between microbicide researchers, public-health workers and advocacy organisations.There will be an opening ceremony on the evening of Sunday 28 March at which politicians, policy makers and the international media are expected. The conference will run for a full three days, each of which will contain:Scientific overviews and presentations with plenary sessions, invited lecturers and presentations of original researchWorkshops to review issues unique to microbicides such as trial design and outcome measures, and ethical issues in the clinical trials of microbicidesPoster sessions. Focus on LondonFollowing the successful Microbicides conferences in Washington in 2000 and Antwerp in 2002, March 2004 sees the focus move to London.The venue is the Hilton Metropole Hotel, two minutes by taxi from Paddington station and the Heathrow Express, with a journey time from the airport of 15 minutes. The hotel is in walking distance of Hyde Park and London’s main shopping streets, and close to Imperial College. Accommodation will be available at the venue and other hotels in the vicinity.London in March offers a variety of diversions for out-of-conference relaxation, including sight-seeing and shopping; the arts and the theatre; and pubs, clubs and restaurants to suit every taste. Conference staff will be on hand to help delegates plan their spare time.To book your place or find out more information, e-mail info@microbicides2004.org.uk or telephone the Event Office on +44 (0) 20 7720 4411
Oral: invited speaker Oral: Track A Oral: Track B Oral: Track C Poster: Track A Poster: Track B Poster: Track C Abstract only Authors

02202 STRUCTURAL STUDIES OF APTAMERS THAT NEUTRALIZE R5 SRTAIN OF HIV-1

Dey, Antu*, **
Khati, M.**, Lea, S.*, James, W.**
* Laboratory of Molecular Biophysics, Department of Biochemistry, ** Sir William Dunn School of Pathology, South Parks Road, University of Oxford, Oxford, UK.

Human Immunodeficiency Virus 1(HIV-1) has evolved various strategies in response to the current anti-retroviral drugs and the selection pressure of humoral and cellular immunity. In particular, the R5 strains of HIV that is central to Acquired Immune Deficiency Syndrome (AIDS) pathogenesis are resistant to neutralization by antibodies. The recessed nature of the binding pockets on the surface glycoprotein (gp120), masking by hypervariable loops, conformational changes in the core gp120 molecule and a ‘glycan shield’ mechanism of neutralization escape allow HIV-1 persistence in the face of an evolving antibody repertoire. We hypothesized that RNA aptamers, in contrast to antibodies, by virtue of their small size and slow dissociation rates, might be able to bind to the occluded neutralization sites on the gp120. Accordingly, using Systematic Evolution of Ligands by EXponential Enrichment (SELEX), we have isolated specific 2’Fluoro-pyrimidine RNA aptamers that bind to monomeric HIV-1BaL gp120 with affinities in the order of 10-9 M. The aptamers not only neutralize HIV-1BaL in human Peripheral Blood Mononuclear Cells (PBMCs) by 1,000- to 100,000-fold but also neutralize clinical isolates from multiple clades efficiently. Secondary structure analysis, in conjunction with ribonuclease footprinting studies, revealed the probable region essential for gp120-binding. Truncating the aptamer to this smaller region retained its binding to monomeric gp120. The binding affinity and the neutralization potency of the truncated aptamer and the parental aptamer have been found to be similar. Further investigation of the structure of the truncated aptamer might lead to alternative anti-HIV-1 drugs and help us understand the molecular interaction between the viral gp120 and host cellular receptors that facilitate HIV-1 entry.

Mr. Antu Dey
William James’ Lab, Sir William Dunn School of Pathology, South Parks Road, University of Oxford, Oxford, OX1 3RE, UK
(Telephone) 01865-275545 (Fax) 01865-285756 (E-mail) antu.dey@bioch.ox.ac.uk