Important note: Information in this article was accurate in May 2001. The state of the art may have changed since the publication date.
American Foundation for AIDS Research, May 2001
Jo Ann Berg
Research into microbicides, which could be topically applied to vagina or rectum to prevent HIV transmission, continues to make slow headway. At Keystone, James Hildreth of the Johns Hopkins University School of Medicine presented preliminary findings of a promising microbicide called b-cyclodextrin .1 Widely used as food additives, cyclodextrins are derived from the partial breakdown of starch.
Hildreth's lab discovered that HIV particles bud from infected cells only at special points on the cellular membrane known as "lipid rafts." Lipid rafts are particularly rich in cholesterol, which is important for membrane fluidity. HIV takes along this cholesterol as part of the cellular membrane it carries away from its source cell. Without this cholesterol, HIV cannot fuse with new cells. Conversely, cells without cholesterol in their membranes are impervious to HIV.
A cholesterol-depleting compound like b-cyclodextrin might have microbicidal potential. Hildreth's lab tested this premise in mice reconstituted with human vaginal cells and found that b-cyclodextrin significantly inhibited HIV without vaginal toxicity. In a comparison test between b-cyclodextrin and nonoxynol-9, the researchers found that almost every vaginal epithelial cell was killed by nonoxynol-9 and virtually none by b-cyclodextrin.
Edward Burger of the National Institutes of Health described another novel microbicide approach. .2 His candidate microbicide consists of an experimental protein containing a soluble CD4 receptor tethered to an antibody that can neutralize HIV. The CD4 receptor initially binds to the HIV envelope protein (gp120) as if the virus had come in contact with the CD4 receptors on one of its target cells. This causes the gp120 to open up, exposing the sections of envelope critical to cell entry. The antibody can then bind to one of the newly exposed envelope regions and eliminate its ability to bind to the cell. Berger claimed that his molecule could be produced for "pennies per dose" by bioengeneered plants. Alternatively, the lactobacilli bacteria that form part of the normal, healthy vaginal flora could be genetically manipulated to express this molecule on their surface. The result would be a kind of "viral flypaper."
1. Hildreth JFK, "Adhesion Molecules, Lipid Rafts and HIV Pathogenesis", HIV Pathogenesis Keystone Symposium. March 28-April 3, 2001; oral presentation 038
2. Berger EA, "Receptor-Based Intervention Strategies", HIV Pathogenesis Keystone Symposium. March 28-April 3, 2001; oral presentation 031.
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