Kemri-Wellcome Trust Research Programme: Molecular and functional analysis of antibody repertoire and proviral DNA in HIV-1 exposed seronegative individuals

Mucosal antibodies to HIV have been previously reported in HIV exposed seronegative individuals. In the pilot phase of a previous study, Iwe detected gp140 IgG inserum from of one out of five high-risk individuals, and memory B cells that upon polyclonal expansion produced IgA and IgG against gp140. We are now in the process of screening a cohort of 200 high-risk individuals for similar responses. In the proposed study, I will assess gp140 specific antibodies fromserum and from polyclonal expansion of the memory B cell pool in culture for the ability to neutralize different HIV strains, and for the ability to mediate Fc-R mediated functions such as ADCC, ADCVI, phagocytosis and complement fixation. These assays will allow us to establish whether the detected anti-HIV-1 antibodies can prevent infection either through neutralisation of the virus or through Fcdependent mechanisms. In addition, I will test whether or not we can detect HIV-1 pro-viral DNA in resting CD4 cells of ESN indicating transient or latent infection. If I can identify proviral DNA, I will sequence it to assess sequence homogeneity and to compare neutralising antibody activity to cognate HIV-1 antigen and antigenrepresenting other strains as proof or antibody escape.

Programme: International Masters Fellowship

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