Background

The majority of heterosexual transmission of HIV-1 occurs at the site of the genital tract. This is the first site of exposure to HIV in the majority of instances and immune responses at mucosal surfaces are likely to be critical in mediating protection against infection. Vaccination strategies that induce strong mucosal as well as systemic responses show promise in macaque models of HIV pathogenesis. Indeed, HIV specific effector immune responses at the mucosal surface are detectable in a high proportion of individuals who are resistant to HIV despite repeated exposure. HIV specific IFN-? secreting CD8+ T cells have been detected in approximately half of HIV resistant women from a highly exposed population of sex workers in Nairobi, Kenya. As well, HIV specific IgA capable of neutralising a broad range of HIV isolates, and capable of inhibiting HIV transcytosis across epithelial surfaces has been detected in 70% of HIV resistance sex workers. To further understand the role of mucosal immunity in mediating resistance to HIV infection we are continuing studies among HIV resistant sex workers from our cohort in Kenya to:

Objectives

Further characterize the novel epitope recognised by IgG1b12:

1. Characterize T helper cell numbers and responses in genital tract mucosa.
2. Characterise the vaginal proteome to identify biomarkers associated with resistance
3. Correlate these responses with immunogenetic profiles of HIV resistant women.