The recent successful trial of tenofovir vaginal gel provides important proof of concept indicating that a vaginal microbicide can prevent HIV. However, the limited protection observed (39% overall), argues for the development of additional microbicide agents and methods to deliver them. This IPCP application will develop a monoclonal antibody (Mab) based microbicide, distinct from the small molecule antiretrovirals that dominate the current microbicide pipeline. Mabs show promise in providing safe, potent, and specific, yet broad-spectrum microbicide action. Project 4 will attempt to enhance Mab effectiveness by its focus on the means of Mab delivery. Limitations on microbicide effectiveness can be divided into two categories: first, intrinsic failure of the method to provide protection when used (

Public Health Relevance

We propose to develop new ways to deliver microbicides to the vagina that will be more convenient, more long lasting, and more effective than previous methods. The microbicide we will deliver is composed of antibodies, which are substances naturally used by the human immune system to block infections. The antibodies will be delivered using a vaginal ring, or a vaginal diaphragm, which is a ring plus an attached cup-like dome that covers and protects the cervix.

Agency
National Institute of Health (NIH)
Institute
National Institute of Allergy and Infectious Diseases (NIAID)
Type
Research Program--Cooperative Agreements (U19)
Project #
5U19AI096398-03
Application #
8515321
Study Section
Special Emphasis Panel (ZAI1-ESB-A)
Project Start
Project End
Budget Start
2013-08-01
Budget End
2014-07-31
Support Year
3
Fiscal Year
2013
Total Cost
$78,500
Indirect Cost
Name
Boston University
Department
Type
DUNS #
604483045
City
Boston
State
MA
Country
United States
Zip Code
02118
Wang, Y-Y; Kannan, A; Nunn, K L et al. (2014) IgG in cervicovaginal mucus traps HSV and prevents vaginal herpes infections. Mucosal Immunol 7:1036-44
Whaley, Kevin J; Morton, Josh; Hume, Steve et al. (2014) Emerging antibody-based products. Curr Top Microbiol Immunol 375:107-26
Anderson, Deborah J; Marathe, Jai; Pudney, Jeffrey (2014) The structure of the human vaginal stratum corneum and its role in immune defense. Am J Reprod Immunol 71:618-23
McKinley, Scott A; Chen, Alex; Shi, Feng et al. (2014) Modeling neutralization kinetics of HIV by broadly neutralizing monoclonal antibodies in genital secretions coating the cervicovaginal mucosa. PLoS One 9:e100598
Chen, Alex; McKinley, Scott A; Wang, Simi et al. (2014) Transient antibody-mucin interactions produce a dynamic molecular shield against viral invasion. Biophys J 106:2028-36
Gunawardana, Manjula; Baum, Marc M; Smith, Thomas J et al. (2014) An intravaginal ring for the sustained delivery of antibodies. J Pharm Sci 103:3611-20
O'Hanlon, Deirdre E; Moench, Thomas R; Cone, Richard A (2013) Vaginal pH and microbicidal lactic acid when lactobacilli dominate the microbiota. PLoS One 8:e80074