I am a viral immunologist studying the requirements for an effective host response to viral infection. I am also investigating the potential for the development of efficacious vaccines to protect against infection and ways of intervening in the disease pr
Characterisation and Stability of ISCOM Vaccines. ISCOMS® are particles comprising saponin, cholesterol and phospholipids which when mixed with proteins form potent vaccines. When proteins are associated with ISCOMs® a variety of different sized particles with various surface chemistries can be formed. This project aims to understand the physico-chemical mechanisms governing ISCOM® formation. This understanding will allow development of methods for controlling the size, characteristics and long- ....Characterisation and Stability of ISCOM Vaccines. ISCOMS® are particles comprising saponin, cholesterol and phospholipids which when mixed with proteins form potent vaccines. When proteins are associated with ISCOMs® a variety of different sized particles with various surface chemistries can be formed. This project aims to understand the physico-chemical mechanisms governing ISCOM® formation. This understanding will allow development of methods for controlling the size, characteristics and long-term stability of these particles. In addition the size and surface chemistry of the particles will be correlated with their effectiveness as vaccines. Both these outcomes will support the ongoing commercial development of ISCOM®-based vaccines at CSL.Read moreRead less
Development of purified antibodies that kill virus infected cells. This proposal will develop panels of purified and monoclonal antibodies that kill virus infected cells. These antibodies may show efficacy in preventing HIV infection. This is new technology that could subsequently be harnessed to protect or limit the devastating effects of chronic viruses such as HIV.
Enhancing immunogenicity of DNA vaccines by targeted delivery to antigen presenting cells. Vaccines have proven to be one of the most effective means of preventing infection and also provide promise as a treatment for cancer. However, the range of effective technologies that make possible the delivery of vaccines that can protect against a broad range of infections is limited. DNA based vaccines are attractive because they are relatively easy to produce against a wide range of infections. Howeve ....Enhancing immunogenicity of DNA vaccines by targeted delivery to antigen presenting cells. Vaccines have proven to be one of the most effective means of preventing infection and also provide promise as a treatment for cancer. However, the range of effective technologies that make possible the delivery of vaccines that can protect against a broad range of infections is limited. DNA based vaccines are attractive because they are relatively easy to produce against a wide range of infections. However, DNA vaccines often provide poor protection against infections. This project will explore a unique technology developed in Australia and that will greatly improve the effectiveness of DNA vaccines against a broad range of diseases. Read moreRead less
HIV currently infects ~40 million people world-wide, causing ~3 million deaths in 2003, mainly in the world's poorest countries. A cheap, effective vaccine seems the best means of preventing the spread of the epidemic. The two main approaches to vaccination are either to make antibodies (which bind to and inactivate the virus), or killer T cells (which kill infected cells). Many of these vaccines are now being tested in monkeys. The results of killer T cell vaccination trials have been both enco ....HIV currently infects ~40 million people world-wide, causing ~3 million deaths in 2003, mainly in the world's poorest countries. A cheap, effective vaccine seems the best means of preventing the spread of the epidemic. The two main approaches to vaccination are either to make antibodies (which bind to and inactivate the virus), or killer T cells (which kill infected cells). Many of these vaccines are now being tested in monkeys. The results of killer T cell vaccination trials have been both encouraging and disappointing. The vaccines do not appear able to prevent the monkeys from getting infected with the virus. However, in many cases even though the monkeys become infected with HIV, they do not get the usual disease associated with AIDS, and hence live with rather than die from this infection. The aims of this project are to use statistical analysis, and more complex mathematical and computer models to try to analyse the data generated by these vaccine trials and to understand how these partially effective vaccines help control virus. For example, even if a vaccine does not prevent infection, we can investigate whether it slowed viral growth, or increased killing of infected cells, and if so, whether an increase in this response could be effective. In preliminary work we have analysed data from a vaccination trial performed in Boston. The results of this study suggest that the reason vaccinated monkeys still become infected is that the killer T cells produced by the vaccine do not appear to activate for the first 10 days of infection. In these first 10 days the virus grows normally and is able to establish a foothold for continuing infection. By contrast, we find that antibodies act extremely early after infection. The methods we propose have not been used before to study vaccines, and by studying the kinetics of the virus and immune response from a large number of vaccine trials we hope to help identify the optimal vaccine design.Read moreRead less