We are using molecular biology, microbiology and protein engineering to develop a new type of preventative for HIV infection. Our approach uses live microbes that secrete anti-HIV peptides onto the mucosal surfaces where sexual transmission of HIV occurs. We have demonstrated the feasibility of this live microbicide approach by genetically engineering commensal strains of both rectal and vaginal bacteria to secrete high levels of HIV fusion inhibitor proteins both in vitro and in vivo. We have now tested the vaginal efficacy of a Lactopbacillus strain producing the HIV inhibitor Cyanovirin and showed that it protects against SHIV infection by greater than 60%. The primate system is also being used to analyze the interrelationships between vaginal microflora, the menstrual cycle, and the innate immune system. A new project involves the development of novel high definition real time video methods to monitoring HIV infection and growth in tissue explants. These will provide a novel assay system for the efficacy of microbicides

Agency
National Institute of Health (NIH)
Institute
National Cancer Institute (NCI)
Type
Investigator-Initiated Intramural Research Projects (ZIA)
Project #
1ZIABC010530-10
Application #
8552725
Study Section
Project Start
Project End
Budget Start
Budget End
Support Year
10
Fiscal Year
2012
Total Cost
$341,324
Indirect Cost
Name
National Cancer Institute Division of Basic Sciences
Department
Type
DUNS #
City
State
Country
Zip Code
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
Lagenaur, Laurel A; Lee, Peter P; Hamer, Dean H et al. (2011) Demonstration of vaginal colonization with GusA-expressing Lactobacillus jensenii following oral delivery in rhesus macaques. Res Microbiol 162:1006-10
Yu, Rosa R; Cheng, Andrew T; Lagenaur, Laurel A et al. (2009) A Chinese rhesus macaque (Macaca mulatta) model for vaginal Lactobacillus colonization and live microbicide development. J Med Primatol 38:125-36
Grant, Robert M; Hamer, Dean; Hope, Thomas et al. (2008) Whither or wither microbicides? Science 321:532-4
Tao, Wang; Richards, Chris; Hamer, Dean (2008) Enhancement of HIV infection by cellulose sulfate. AIDS Res Hum Retroviruses 24:925-9