: Osel was founded to develop and commercialize a novel approach to prevent vaginal HIV transmission in women. We propose to create bifunctional proteins containing an HIV-binding domain (CD4) and a lactobacillus-binding domain. Such bifunctional proteins will multivalently crosslink HIV to the lactobacilli abundantly resident on the mucosal microflora, thus preventing immobilized viral particles from progressing to infect underlying host cells. Bound viruses may be inactivated by either hydrogen peroxide produced by lactobacilli or removed from the body by normal sloughing of mucosal bacteria. Thus, application of such bifunctional proteins onto the vaginal mucosa up to 24 hours before vaginal intercourse should significantly reduce the number of available HIV particles introduced by semen, thereby reducing or eliminating the risk of viral transmission. This novel approach would create a novel barrier to viral transmission that is different from traditional approaches. Therefore, it should act synergistically with vaccines, condoms, or other potential methods of protection. The underlying concept is generally applicable to other viruses that infect at other anatomical sites, such as respiratory or intestinal mucosa. The work being proposed include (i) selection of lactobacilli-specific binding peptides (LSP) via combinatorial phage display libraries followed by their genetic transfer to the soluble CD4 protein to create bifunctional CD4-LSP proteins, and (ii) testing the ability of such bifunctional proteins to neutralize HIV in vitro in the presence of lactobacilli.
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