Development of a live topical microbicide for women

Osel is developing a live microbicide, employing H2O2-producing Lactobacillus jensenii 1153, a natural component of human vaginal microflora, as a delivery vehicle.

An expression cassette harboring native regulatory elements was optimized to secrete high levels of modified cyanovirin-N (P51G) (CV-N). The expression cassette was stably integrated into the bacterial chromosome.

The CV-N-producing L. jensenii retained important characteristics of the native bacterial phenotype and secreted high levels of full-length CV-N that completely inhibited the infectivity of CCR5-tropic HIVBaL in vitro, with an IC50 near 1 nM. We further demonstrated that this strain was capable of association with epithelial cells in the vaginal lumen of CD-1 mice, and expressed CV-N in vivo in this model and when cultured in cervicovaginal lavage fluid of pigtailed macaques. We are evaluating potential regulatory issues, bacterial formulations, vaginal colonization, in situ CV-N expression, and host immunological responses in non-human primate models.

This work represents a major step towards the development of a simple, cost-effective, female-controlled preventative against heterosexual transmission of HIV.

Supported by NIH grants U19 AI60615 and U01 AI066708.

Affiliations

1. Osel, Inc., 4008 Burton Dr., Santa Clara, California, 95054, USA
   • Qiang Xu
   • , Laurel Lagenaur
   • , Xiaowen Liu
   • , Yang Liu
   • , Rosa Yu
   • , Kim Wells
   • , Daniel Tsai
   • , Thomas Parks
   •  & Peter Lee
2. Department of Obstetrics and Gynecology, University of Washington, Seattle, Washington, 98195, USA
   • Yvonne Sweeney
   •  & Dorothy Patton
3. Laboratory Animal Medicine, National Institutes of Health, Bethesda, Maryland, 20892, USA
   • Srinivas Rao
4. National Cancer Institute, National Institutes of Health, Bethesda, Maryland, 20892, USA
   • Dean Hamer

Corresponding author

Correspondence to Qiang Xu.

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