This proposal outlines the development of a novel live microbicide, termed MucoCept, designed to prevent heterosexual HIV transmission in women. MucoCept is an H2O2- producing vaginal L. jensenii 1153 strain that has been genetically modified to constitutively secrete a potent anti-HIV protein, cyanovirin-N (CV-N). We propose to assess the safety, tolerability and affect on innate genital tract immune factor and colonization following application of a CV-N expressing L. jensenii designated 1153- 1666 using the Non-Human Primate model. In addition, we will assess and confirm the clearance of the L. jensenii 1153-1666 strain in the Non-Human primate following antibiotic administration.

Public Health Relevance

We are assessing the feasibility of a recombinant human Lactobacillus to serve as a topical microbicide to prevent HIV transmission in women. A human vaginal strain of L. jensenii has been genetically enhanced that is capable of persistently colonizing the vaginal mucosa and constitutively secreting a protein that prevents HIV entry, thus protecting women from HIV transmission via vaginal intercourse.

Agency
National Institute of Health (NIH)
Institute
National Institute of Allergy and Infectious Diseases (NIAID)
Type
Exploratory/Developmental Grants Phase II (R33)
Project #
5R33AI071978-05
Application #
8126267
Study Section
Special Emphasis Panel (ZAI1-RB-A (M1))
Program Officer
Turpin, Jim A
Project Start
2007-09-30
Project End
2013-08-31
Budget Start
2011-09-01
Budget End
2013-08-31
Support Year
5
Fiscal Year
2011
Total Cost
$364,466
Indirect Cost
Name
Osel, Inc.
Department
Type
DUNS #
017444147
City
Mountain View
State
CA
Country
United States
Zip Code
94043
Lagenaur, Laurel A; Swedek, Iwona; Lee, Peter P et al. (2015) Robust vaginal colonization of macaques with a novel vaginally disintegrating tablet containing a live biotherapeutic product to prevent HIV infection in women. PLoS One 10:e0122730
Brichacek, Beda; Lagenaur, Laurel A; Lee, Peter P et al. (2013) In vivo evaluation of safety and toxicity of a Lactobacillus jensenii producing modified cyanovirin-N in a rhesus macaque vaginal challenge model. PLoS One 8:e78817
Hemmerling, Anke; Cohen, Craig R (2011) Probiotics: the potential for a live microbicide to prevent HIV. J Acquir Immune Defic Syndr 56:e98-101
Lagenaur, L A; Sanders-Beer, B E; Brichacek, B et al. (2011) Prevention of vaginal SHIV transmission in macaques by a live recombinant Lactobacillus. Mucosal Immunol 4:648-57