Retrovirology

, 2:S93 | Cite as

Development of Vaginal Lactobacilli for Mucosal Delivery of a Topical Microbicide, Cyanovirin-N (CV-N)

  • Laurel Lagenaur
  • Xiaowen Liu
  • David A Simpson
  • Kirsten Essenmacher
  • Courtney Parker
  • Chia-Hwa Chang
  • Daniel Tsai
  • Srinivas Rao
  • Dean Hamer
  • Thomas P Parks
  • Peter P Lee
  • Qiang Xu
Open Access
Oral presentation

Keywords

Lactobacillus Antibiotic Resistance Single Copy Expression Cassette Delivery Vehicle 

Background

Women are particularly at risk of HIV infection, therefore, female initiated strategies are essential to curtail the HIV/AIDS pandemic worldwide.

Material and Methods

We developed a live topical microbicide, which is an H2O2-producing Lactobacillus jensenii, a natural component of the vaginal microflora, as a delivery vehicle for the potent HIV inhibitor, cyanovirin-N (CV-N).

Results

The optimized CV-N expression cassette was stably integrated in single copy into the lactobacillus bacterial chromosome, and resolved from extraneous plasmid DNA and antibiotic resistance determinants. The L. jensenii-expressed CV-N dramatically decreased CCR5-trophic HIVBaL infectivity in vitro, with an IC50 of 0.3 nM. Histological examination of CD1 mice, which were intra-vaginally inoculated with L. jensenii expressing CV-N, revealed that L. jensenii was associated with keratinized epithelium present during estrus or free in the vaginal lumen and secreted full-length CV-N in vivo.

Conclusion

This live microbicide represents a major step towards developing inexpensive, durable protein-based microbicides to address the urgent need for female-controlled approaches to block the heterosexual transmission of HIV.

Copyright information

© The Author(s) 2005

Authors and Affiliations

  • Laurel Lagenaur
    • 1
  • Xiaowen Liu
    • 1
  • David A Simpson
    • 1
  • Kirsten Essenmacher
    • 1
  • Courtney Parker
    • 1
  • Chia-Hwa Chang
    • 1
  • Daniel Tsai
    • 1
  • Srinivas Rao
    • 2
  • Dean Hamer
    • 3
  • Thomas P Parks
    • 1
  • Peter P Lee
    • 1
    • 4
  • Qiang Xu
    • 1
  1. 1.Osel, Inc.1800 Wyatt Dr., Ste. 14Santa ClaraUSA
  2. 2.Laboratory Animal Medicine, VRC, NIHBethesdaUSA
  3. 3.National Cancer Institute, NIHBethesdaUSA
  4. 4.Dept. of MedicineStanford UniversityStanfordUSA

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