Antibody dependent cellular cytotoxicity (ADCC) - a neglected anti-HIV immune response!
The importance of HIV-specific Antibody-dependent Cellular Cytotoxicity (ADCC) antibodies that inhibit viral replication mediated through the Fc receptor is becoming clear. In view of the difficulty of inducing broad neutralising antibodies and effective T cell immunity, exploring HIV-specific ADCC is a priority. HIV-specific ADCC has been under-explored both from the point of view of rapid, reliable assays to measure and characterise ADCC responses and the ability to specifically induce high level HIV-specific ADCC antibodies by vaccination. Recent data from the RV144 vaccine study in Thailand suggest a role for non-neutralising antibodies in protection from HIV.
Combined Influenza-AIDS Vaccines
Influenza and HIV are both serious global pathogens. Can a single vaccine be designed to cover both viruses? Recent advances in reverse genetic techniques allow insertion of foreign antigens into live influenza viruses. Further, live attenuated influenza vaccines are now highly effective vaccines. Stephen’s group is designing recombinant influenza vaccines with inserted HIV antigens to test as a combined Influenza-AIDS vaccine. An advantage of this strategy is that as a mucosal virus, there is a strong likelihood that immunity at mucosal surfaces, where HIV is first encountered, can be induced with this approach.
Nanoparticle HIV vaccines
No safe HIV vaccines have been able to stimulate durable, activated T-cell immunity. Stephen’s group is investigating an exciting HIV vaccination approach using hollow, submicron, delivery vehicles (nanocapsules) as carriers for HIV vaccines. This is a novel, cross-disciplinary project within the Australian Research Council (ARC) Centre of Excellence in Bio-Nano interactions. Nanocapsules are designed to induce optimal immune responses by protecting antigens from degradation prior to reaching sites of immune activation and activate antigen presenting cells in a way that will initiate anti-viral immune responses. Stephen’s group aims to use controlled-release nanocapsules to stimulate durable anti-HIV responses in vivo.
NKT cells, MAIT cells and HIV
NKT cells are a small but very important lymphocyte population in blood that possess potent antiviral and antitumor activities. NKT cells are depleted during HIV infection. Stephen’s group are now devising strategies to enhance the biologic utility of NKT cells in fighting HIV. They are also starting to study an interesting population of cells called Mucosal-associated Invariant T cells (MAIT cells). MAIT cells are likely to be important in protecting HIV-infected people from damage at mucosal surfaces such as the gut.
Checkmating HIV - trapping immune escape HIV strains
CD8+ cytotoxic T lymphocytes (CTL) can be effective at controlling HIV-1, but their utility is partly offset by mutational escape. The kinetics of CTL escape, and reversion of escape mutant viruses upon transmission to MHC-mismatched hosts can help understand CTL-mediated viral control and the fitness cost extracted by immune escape mutation. The work has implications for how best to control HIV during early infection.
Influenza – specific ADCC: role in a Universal Flu vaccine?
Influenza mutates regularly to avoid neutralising antibodies. Immune responses targeting more conserved areas are needed to combat new flu pandemics. Stephen’s group have adapted and refined their HIV ADCC assays to study Influenza. They have found there is a remarkable degree of cross-reactivity in influenza ADCC immunity. They recently found that influenza ADCC can play a role in reducing the severity of the 2009 Swine Flu epidemic. The work opens up a whole new field of flu immunity. They are now studying how flu-specific ADCC can be induced by vaccination and lead to protective immunity.
Professor Stephen Kent trained as an infectious diseases physician and viral immunologist in Melbourne and the USA. He is a National Health and Medical Research Council Principal Research Fellow. Stephen heads a lab studying immunity to HIV and other variable and difficult to vaccinate against viruses. Several vaccine concepts tested in his lab have shown sufficient promise to progress into human clinical trials. Stephen remains active in infectious diseases clinical medicine caring for people with HIV.