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.
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.
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 |