Details

Autor(en) / Beteiligte

• Moore, John P
• Klasse, Per Johan
• Schader, Susan M
• Marx, Preston A
• Dufour, Jason
• Colonno, Richard J
• Ketas, Thomas J
• Hu, Qinxue
• Lu, Min
• Shattock, Robin J
• Springer, Martin S
• Veazey, Ronald S

Titel

Protection of macaques from vaginal SHIV challenge by vaginally delivered inhibitors of virus-cell fusion

Ist Teil von

• Nature, 2005-11, Vol.438 (7064), p.99-102

Ort / Verlag

London: Nature Publishing

Erscheinungsjahr

2005

Quelle

PBSC : Psychology and Behavioral Sciences Collection - Journals

Beschreibungen/Notizen

• 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.