Nature advance online publication;
published online 30 October 2005 | doi: 10.1038/nature04055
Protection of macaques from vaginal SHIV
challenge by vaginally delivered inhibitors of virus–cell fusion
Ronald S. Veazey1, Per
Johan Klasse2, Susan M. Schader2, Qinxue Hu3,
Thomas J. Ketas2, Min Lu4, Preston A. Marx1,
Jason Dufour1, Richard J. Colonno5, Robin J.
Shattock3, Martin S. Springer6 and John P. Moore2
Human immunodeficiency virus type 1
(HIV-1) continues to spread, principally by heterosexual sex, but no
vaccine is available1. 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 intercourse2. 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 receptors3, 4, CMPD167,
a small molecule that binds to CCR5 to inhibit gp120 association5, and
C52L, a bacterially expressed peptide inhibitor of gp41-mediated
fusion6. 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.
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1. Tulane National Primate Research
Center, Covington, Louisiana 70433, USA
2. Department of Microbiology and
Immunology, Weill Medical College of Cornell University, New York, New
York 10021, USA
3. St George's, University of
London, London SW17 0RE, UK
4. Department of Biochemistry, Weill
Medical College of Cornell University, New York, New York 10021,
USA
5. Bristol-Myers Squibb
Pharmaceutical Institute, Wallingford, Connecticut 06492, USA
6. Merck Research Laboratories,
Rahway, New Jersey 07065, USA
Correspondence to: John P. Moore2
Correspondence should be addressed to J.P.M. (Email:
jpm2003@med.cornell.edu); see Supplementary Information for details
about requests for materials.