%0 Journal Article
%T Differential activity of candidate microbicides against early steps of HIV-1 infection upon complement virus opsonization
%A Mohammad-Ali Jenabian
%A H¨¦la Sa£¿di
%A Charlotte Charpentier
%A Hicham Bouhlal
%A Dominique Schols
%A Jan Balzarini
%A Thomas W Bell
%A Guido Vanham
%A Laurent B¨¦lec
%J AIDS Research and Therapy
%D 2010
%I BioMed Central
%R 10.1186/1742-6405-7-16
%X We herein evaluated the effect of HIV-1 complement opsonization on microbicide candidates' activity, by using three in vitro mucosal models: CCR5-tropic HIV-1JR-CSF transcytosis through epithelial cells, HIV-1JR-CSF attachment on immature monocyte-derived dendritic cells (iMDDC), and infectivity of iMDDC by CCR5-tropic HIV-1BaL and CXCR4-tropic HIV-1NDK. A panel of 10 microbicide candidates [T20, CADA, lectines HHA & GNA, PVAS, human lactoferrin, and monoclonal antibodies IgG1B12, 12G5, 2G12 and 2F5], were investigated using cell-free unopsonized or opsonized HIV-1 by complements. Only HHA and PVAS were able to inhibit HIV trancytosis. Upon opsonization, transcytosis was affected only by HHA, HIV-1 adsorption on iMDDC by four molecules (lactoferrin, IgG1B12, IgG2G5, IgG2G12), and replication in iMDDC of HIV-1BaL by five molecules (lactoferrin, CADA, T20, IgG1B12, IgG2F5) and of HIV-1NDK by two molecules (lactoferrin, IgG12G5).These observations demonstrate that HIV-1 opsonization by complements may modulate in vitro the efficiency of candidate microbicides to inhibit HIV-1 infection of mucosal target cells, as well as its crossing through mucosa.Recent disappointing failure in microbicide clinical trials revealed that major gaps in basic and applied knowledges remain to conceive effective microbicide formulations [1-3]. In particular, the failure of phase II/III essays on candidate molecules having crossed successfully all the previous stages of the preclinical development, emphasizes the absolute necessity to establish a correlation between the preclinical criteria and the clinical criteria of microbicide molecules development [3]. Thus, one of the major objectives of in vitro evaluation of microbicide candidate molecules during their preclinical development is to get closer as much as possible to physiological conditions.The inhibitory power of microbicide molecules may be affected by semen factors when male and female genital secretions are mixed during sexual in
%U http://www.aidsrestherapy.com/content/7/1/16