HIV vaccine immunogen design
The HIV-1 envelope glycoproteins (Env) are the only targets of neutralizing antibodies, and are the focus of strategies to design a protective vaccine. Env is a heavily glycosylated protein that has multiple immune evasion features including unwanted epitope immunodominance, conformational instability and a glycan sheild that protects the underlying protein surface from B cell recognition. We are applying post-translational chemical modification to Env to reduce its immune evasion characteristics by: i) using chemical cross-linking approaches to stabilise soluble recombinant forms of the Env trimer; ii) site-specific conjugation of glycans to Env antigens to selectively enhance their immunogenicity. Both of these approaches may be combined to generate more effective vaccine designs.
Cell-cell HIV-1 spread
We are studying how HIV-1 spreads between its target cells – CD4 T cells and macrophages – by taking advantage of direct cell-cell contact via structures that we and others have called virological synapses. We are currently attempting to define how HIV-1 spreads between HIV-21-infected CD4 T cells and macrophages across a 'phagocytic synapse', and are focusing on the modulation of 'eat-me' and 'don't eat-me' signals on the surface of infected T cells and their recognition by macrophages.