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  • Oral presentation
  • Open Access

Development of a live topical microbicide for women

  • 1Email author,
  • 1,
  • 1,
  • 1,
  • 1,
  • 1,
  • 1,
  • 2,
  • 3,
  • 4,
  • 2,
  • 1 and
  • 1
Retrovirology20063 (Suppl 1) :S37

https://doi.org/10.1186/1742-4690-3-S1-S37

  • Published:

Keywords

  • Lactobacillus
  • Expression Cassette
  • Lavage Fluid
  • Delivery Vehicle
  • Regulatory Issue

Background

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

Materials and methods

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.

Results

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.

Conclusion

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

Declarations

Acknowledgements

Supported by NIH grants U19 AI60615 and U01 AI066708.

Authors’ Affiliations

(1)
Osel, Inc., 4008 Burton Dr., Santa Clara, California 95054, USA
(2)
Department of Obstetrics and Gynecology, University of Washington, Seattle, Washington 98195, USA
(3)
Laboratory Animal Medicine, National Institutes of Health, Bethesda, Maryland, 20892, USA
(4)
National Cancer Institute, National Institutes of Health, Bethesda, Maryland 20892, USA

Copyright

© Xu et al; licensee BioMed Central Ltd. 2006

This article is published under license to BioMed Central Ltd.

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