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Protection of macaques from vaginal SHIV challenge by vaginally delivered inhibitors of virus-cell fusion | | Ronald S Veazey
; Per Johan Klasse
; Susan M Schader
; Qinxue Hu
; Thomas J Ketas
; Min Lu
; Preston A Marx
; Jason Dufour
; Richard J Colonno
; Robin J Shattock
; Martin S Springer
; John P Moore
; | | Date: |
3 Nov 2005 | | Journal: | Nature, 438 (7064), 99-102 | | Abstract: | Human immunodeficiency virus type 1 (HIV-1) continues to spread, principally by heterosexual sex, but no vaccine is available. Hence, alternative prevention methods are needed to supplement educational and behavioural-modification programmes. One such approach is a vaginal microbicide: the application of inhibitory compounds before intercourse. Here, we have evaluated the microbicide concept using the rhesus macaque ’high dose’ vaginal transmission model with a CCR5-receptor-using simian-human immunodeficiency virus (SHIV-162P3) and three compounds that inhibit different stages of the virus-cell attachment and entry process. These compounds are BMS-378806, a small molecule that binds the viral gp120 glycoprotein and prevents its attachment to the CD4 and CCR5 receptors, CMPD167, a small molecule that binds to CCR5 to inhibit gp120 association, and C52L, a bacterially expressed peptide inhibitor of gp41-mediated fusion. In vitro, all three compounds inhibit infection of T cells and cervical tissue explants, and C52L acts synergistically with CMPD167 or BMS-378806 to inhibit infection of cell lines. In vivo, significant protection was achieved using each compound alone and in combinations. CMPD167 and BMS-378806 were protective even when applied 6 h before challenge. | | Source: | PubMed, pmid16258536 doi: 10.1038/nature04055 | | Services: | Forum | Review | Favorites | |
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