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

02437 HIV NEUTRALIZING IGA OBTAINED BY SCREENING A PHAGE-DISPLAY FAB IGA LIBRARY DERIVED FROM HEPS WOMEN

Bomsel, Morgane
Tudor, D.; Derrien M., Drillet, A.S.; Adam, E.; Houimel, M.; Bouguyon, E. Reynes, J.M.*; Buisson, Y 
Cell Biology Department, Institut Cochin, Paris-France, 75014* Unite de Virologie, Institut Pasteur du Cambodge, Phnom Phenh, Royaume du Cambodge

Backgound: Rare individuals remaining uninfected despite unprotected sex with HIV+ partners, i.e. Highly Exposed Persistently IgG Sero-negative (HEPS), contain in their secretions anti-HIV envelope secretory IgA (S-IgA), suggesting that these S-IgA are involved in protection. Accordingly, such IgA, the major effector molecule of the mucosal immune system, have been shown to inhibit CD4+ cell infection as well as one pathway of HIV entry across mucosa, i.e. transcytosis through an epithelial barrier. Aims: To produce human monoclonal S-IgA targeting conserved HIV envelope epitopes with neutralizing activities. Methods & Results: Cervical secretions from 56 HEPS originated from Cambodia were tested for HIV-envelope glycoprotein S-IgA: 22 contained a high level of anti-HIV envelope gp41 S-IgA. Mucosal B cells of these 22 HEPS were used to construct a combinatorial phage display library expressing Fabs of IgA. Selection for HIV envelope specific Fab was carried out by panning the Fab librairy on immobilized HIV envelope proteins gp41 and peptides covering conserved region of gp41. Several tenth of positive clones were obtained as measured by ELISA and were induced to produce soluble Fab. The Fab were tested for their capacity to block: i) HIV interaction with and trancytosis across epithelial cells; ii) HIV infection of CD4+ cells by different viral strains. Several Fab clone were found to block efficiently HIV transcytosis and infection of CD4+ T cells. Neutralizing Fab will be then used to reconstruct human d-IgA or S-IgA and their precise epitope specificity will be determined. Perspectives: These studies could permit to characterize new neutralizing epitopes on HIV envelope glycoprotein and to dispose of HIV envelope specific IgA clones blocking HIV mucosal entry that could be included in a topical microbicide formulation to prevent mucosal transmission of HIV.

Morgane Bomsel
Institut Cochin, 22 rue Mechain, 75014 Paris
(Telephone) 33 1 40 51 64 97 (Fax) 33 1 40 51 64 54  (E-mail) bomsel@cochin.inserm.fr