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02465 NATIVE VAGINAL LACTOBACILLI ENGINEERED AS A DELIVERY VEHICLE FOR ANTI-HIV PROTEIN MICROBICIDES Lewicki, John A. The predominant mode of HIV transmission worldwide is via heterosexual contact, with the cervico-vaginal mucosa serving as the main site of viral entry in women. The mucosal surfaces are naturally lined with commensal bacteria, primarily lactobacilli. A deficiency of vaginal lactobacilli is associated with increased HIV acquisition. To address the urgent need for female-controlled approaches to block the heterosexual transmission of HIV, Osel is actively pursuing a novel approach, termed MucoCept. This approach involves genetic modification of a preferred vaginal strain of Lactobacillus, to express HIV-binding proteins. Intravaginal colonization of the MucoCept bacteria should replenish flora and serve to trap and inactivate HIV, thus reducing the efficiency of viral transmission. To date, Osel has expressed the biologically active HIV receptor, human two-domain CD4, as either a secreted or cell wall anchored molecule in a vaginal isolate of L. jensenii, and progressed to have the expression cassettes stably integrated into preferred sites of the bacterial chromosome. The resolved integrants retain the wild-type phenotype. Osel is currently advancing Lactobacillus-based expression systems for anti-HIV protein microbicides, including CD4, cyanovirin-N, and HIV entry inhibitors, as a basis for selecting an optimised MucoCept product for eventual clinical testing. VP, R & D, John A. Lewicki |
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