Vaginal Lactobacilli for Mucosal Delivery of the Anti-HIV Microbicide, Cyanovirin-N (CV-N)

Background

Women are particularly at risk of HIV infection and there is an urgent need for female-controlled approaches to block the heterosexual transmission of HIV.

Material and Methods

Our work is aimed at the development of a simple, cost-effective, female-controlled preventative against heterosexual transmission of HIV in women, based on our previous proof-of-concept study employing a natural component of the vaginal microflora, as a delivery vehicle for the anti-HIV protein (PNAS, 2003, 100:11672-11677).

Results

A human vaginal isolate of Lactobacillus jensenii was engineered, by stable integration of an optimized expression cassette into the bacterial genome, to secrete high levels of the highly potent HIV inhibitor, CV-N. The L. jensenii-expressed CV-N dramatically decreases infectivity of CCR5-tropic HIV_BaL and CXCR4-tropic HIV_IIIB in vitro. We further demonstrate that this strain is genetically stable and can transiently colonize animal vaginal mucosa, while retaining important characteristics of the native bacterial phenotype.

Conclusion

This live microbicide represents a novel approach in the development of an inexpensive and stable protein-based microbicide to curtail the HIV/AIDS pandemic worldwide.