Effective preventative measures are required to halt the spread of HIV by sexual contact. A safe, effective, female-controlled chemical barrier is one of the best approaches for preventing HIV transmission. However, the potentially deleterious effects of these compounds on the vaginal mucosal immune system have not been studied. In fact, little work has been done to define the normal immune system of the genital tract in women and nonhuman primates. It is clear that a local immune response to vaginally administered antigens occurs in women and rhesus macaques and that the cellular components of a local immune system are present in the lower genital tract of both women and rhesus macaques. Because vaginal contraceptives containing large amounts of nonoxynol-9 have been associated with significant vaginal irritation, it is important to assess the effect of these products on the local immune system of the vagina and on the cellular components of the vaginal mucosa. This project will use the rhesus macaque model to assess the effect of antimicrobial vaginal products on the levels of total and antigen specific IgA and IgG in vaginal secretions of rhesus macaques. In addition, the project will define the inflammatory changes in the vaginal mucosa that may be associated with use of these products and determine if the inflammation is associated with changes in the components of cell-mediated immunity in the genital tract. To accomplish these goals, we will use ELISA and Western blot assays to determine total and antigen-specific immunoglobulin levels in the vaginal secretions and cellular immunology as says to define the vaginal immune system the of normal rhesus macaques throughout the menstrual cycle. To determine the effect of vaginal microbicides on the vaginal immune system, we will use similar assays to on secretions and tissues from vaginally immunized and SIV-infected rhesus macaques exposed to vaginal microbides. We also use standard histology and immunohistochemistry to define any vaginal mucosal lesions that are induced in rhesus macaques exposed to these products. This project will be generate significant new data regarding the effect of the menstrual cycle and vaginal microbicides on genital tract immune responses. It is hoped that this work will lead to the development of safe barrier methods that prevent the sexual transmission of HIV.
| Miller, Christopher J; Shattock, Robin J (2003) Target cells in vaginal HIV transmission. Microbes Infect 5:59-67 |
| Lu, Fabien X; Ma, Zhongmin; Moser, Susie et al. (2003) Effects of ovarian steroids on immunoglobulin-secreting cell function in healthy women. Clin Diagn Lab Immunol 10:944-9 |
| Miller, Christopher J; Lu, Fabien X (2003) Anti-HIV and -SIV immunity in the vagina. Int Rev Immunol 22:65-76 |
| Arredondo, J; Xusheng Lu, F; Villinger, F et al. (2000) Antigen-dependent cytokine mRNA expression by individual rhesus macaque T helper cells by flow cytometry. Cell Immunol 201:94-108 |
| Miller, C J (1998) Host and viral factors influencing heterosexual HIV transmission. Rev Reprod 3:42-51 |
