Advancing understanding of HIV pathogenesis and vaccine design
Our current research spans the fields of HIV-1 dissemination, HIV-1 antibody-based vaccine design, and the molecular basis of allergy. We use a multi-disciplinary approach, which includes immunology, virology, chemistry, and cell biology together with cutting-edge imaging techniques to address fundamental questions in HIV biology and allergy. To achieve our goals, we have collaborations and partnerships with local and international research groups and with industry. Our overall aim is that, through this integrated, collaborative approach, we will take discoveries in basic science through to their development and clinical application.
As with several other enveloped viruses, HIV-1 can spread infection either by release of cell-free virus or direct contact-mediated, cell-to-cell spread across virological synapses. We first described the virological synapse for HIV-1 spread between T cells, and between macrophages and T cells. We are continuing this work to better understand how HIV-1 creates long-lived viral reservoirs in resting T cells and macrophages, with the aim of reducing or eliminating this reservoir.
Antibodies provide the only robust correlate of protection from HIV-1 infection, but it is still not known how to protective antibody responses can be elicited by vaccination. To address this, we are using novel chemical approaches to create novel antigens with enhanced antigenicity and immunogenicity. In parallel, we have discovered new adjuvants with enhanced antibody inducing activity.
Oxidative stress chemically modifies proteins that can result in their increased immunogenicity. We have shown that the immune response induced is strongly Th2-biased, eliciting hypersensitivity and allergic-type reactions to otherwise innocuous antigens. For example, allergic sensitization to peanut antigens may by activated by their oxidative modification during dry roasting. The major adduct driving immunogenicity is the reactive carbonyl, and we are currently defining the mechanisms by which reactive carbonyls trigger adaptive immune responses.
J. Allergy and Clinical Immunology 6749: 1031-8.
Cell Host Microbe 16: 711-21.
Nature Biotechnology 30: 883-888.
Plos Pathogens 7: e1002226.
Blood 111: 4660-4663.