Research efforts to develop topical microbicides for intravaginal use for prevention of sexually transmitted infections including HIV have been ongoing for nearly a decade. An estimated 333 million new cases of vaginally and rectally transmitted diseases occur in the world each year according to the World Health Organization. Clearly, an ideal microbicide would prevent the transmission of both vaginally and rectally acquired sexually transmitted infections (STI). Therefore, topical microbicide products must be tested to ensure that the sexual transmission of HIV and other sexually transmitted infections is prevented, and that the vaginal and rectal environments, including the epithelium, are preserved. We have developed a useful model to evaluate the safety of topical microbicide products after vaginal and rectal use in the pigtailed macaque. We have used this model to study the effects of single and repeated applications of microbicides on vaginal and rectal microflora and epithelium. One of the strengths of this macaque model is the similar vaginal microflora shared by the pigtailed macaque and humans. The presence of endogenous lactobacilli, and of H2O2-producing lactobacilli in particular, provides for studies which determine a product's influence on vaginal microbiology and more importantly on the production of H2O2 in the vaginal milieu, which is known to have antimicrobial properties.
The specific aims of this project are to document the colonization and cyanovirin secretion of an optimized lactobacillus product in the macaque model. Additionally, we will use the macaque model to assess the safety of vaginally and rectally applied products developed in this Program. These macaque studies will provide important preclinical data for advancing the Program's topical microbicide product to phase I clinical trials.
| Gupta, Phalguni; Lackman-Smith, Carol; Snyder, Beth et al. (2013) Antiviral activity of retrocyclin RC-101, a candidate microbicide against cell-associated HIV-1. AIDS Res Hum Retroviruses 29:391-6 |
| Gupta, Phalguni; Ratner, Deena; Ding, Ming et al. (2012) Retrocyclin RC-101 blocks HIV-1 transmission across cervical mucosa in an organ culture. J Acquir Immune Defic Syndr 60:455-61 |
| Martellini, Julie A; Cole, Amy L; Svoboda, Pavel et al. (2011) HIV-1 enhancing effect of prostatic acid phosphatase peptides is reduced in human seminal plasma. PLoS One 6:e16285 |
| Li, Ming; Patton, Dorothy L; Cosgrove-Sweeney, Yvonne et al. (2011) Incorporation of the HIV-1 microbicide cyanovirin-N in a food product. J Acquir Immune Defic Syndr 58:379-84 |
| Sassi, A B; Cost, M R; Cole, A L et al. (2011) Formulation development of retrocyclin 1 analog RC-101 as an anti-HIV vaginal microbicide product. Antimicrob Agents Chemother 55:2282-9 |
| Cole, Alexander M; Patton, Dorothy L; Rohan, Lisa C et al. (2010) The formulated microbicide RC-101 was safe and antivirally active following intravaginal application in pigtailed macaques. PLoS One 5:e15111 |
| Venkataraman, Nitya; Cole, Amy L; Ruchala, Piotr et al. (2009) Reawakening retrocyclins: ancestral human defensins active against HIV-1. PLoS Biol 7:e95 |
| Sivaraman, Karthikeyan; Seshasayee, Aswinsainarain; Tarwater, Patrick M et al. (2008) Codon choice in genes depends on flanking sequence information--implications for theoretical reverse translation. Nucleic Acids Res 36:e16 |
| Sorensen, Ole E; Borregaard, Niels; Cole, Alexander M (2008) Antimicrobial peptides in innate immune responses. Contrib Microbiol 15:61-77 |
| Cole, Alexander M; Cole, Amy Liese (2008) Antimicrobial polypeptides are key anti-HIV-1 effector molecules of cervicovaginal host defense. Am J Reprod Immunol 59:27-34 |
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