Novel Generic Vaccine Approaches Applied For The Prevention Of Hepatitis C And Influenza Virus Infections.
Funder
National Health and Medical Research Council
Funding Amount
$392,328.00
Summary
For the induction of good immune responses, antigens should be delivered in several copies on a defined particle. The small envelope protein (HBsAg) encoded by the hepatitis B virus (HBV) has the capacity to self-assemble with host derived lipids into VLPs. HBsAg VLPs are the sole component of one of the most successful vaccines, and clinical trials have shown that they are a successful delivery system for foreign epitopes or protein domains. Hepatitis C virus (HCV) and Influenza viruses are maj ....For the induction of good immune responses, antigens should be delivered in several copies on a defined particle. The small envelope protein (HBsAg) encoded by the hepatitis B virus (HBV) has the capacity to self-assemble with host derived lipids into VLPs. HBsAg VLPs are the sole component of one of the most successful vaccines, and clinical trials have shown that they are a successful delivery system for foreign epitopes or protein domains. Hepatitis C virus (HCV) and Influenza viruses are major human pathogens. HCV has infected 200 million people worldwide, and there is no effective vaccine available. Influenza continues to affect thousands of people each year causing epidemics with severe morbidity and considerable mortality. Current influenza vaccines are mostly inactivated formulations and they exhibit poor immunogenicity in immunological naive persons such as children and in the elderly. The influenza vaccines are not optimal for stimulation of cell-mediated immunity. We propose to use particulate antigens as a delivery platform for influenza and HCV-specific epitopes with the focus to develop approaches to target various HCV and influenza strains, including H5N1 bird influenza. We have successfully produced modified VLPs containing HCV-specific sequences, which are able to induce anti-HCV antibodies with neutralising capacity. We hypothesise that the design of VLPs with an appropriate set of HCV-specific antigens will enhance the neutralising capacity of anti-HCV sera and this may overcome strain specificity. This application will exploit a prototype delivery system to induce antibody and also cellular responses against a variety of HCV- and influenza specific target sequences (epitopes). The outcome of this study will be a prototype multivalent vaccine to a range of HCV- and influenza-specific epitopes. As a delivery system this will be ideal for vaccination against agents that are highly variable.Read moreRead less
Wave slam on high speed wave piercing catamaran ferries in large seas. Australia has taken a pioneering lead in the design of high speed multi-hull ferries and continues to extend their speed, range and payload performance. Design leadership and the technology which supports it are crucial to maintaining the existing large share of the international market for such vessels. Recently freight and military transport vessels have been exposed to much more severe wave conditions than passenger vessel ....Wave slam on high speed wave piercing catamaran ferries in large seas. Australia has taken a pioneering lead in the design of high speed multi-hull ferries and continues to extend their speed, range and payload performance. Design leadership and the technology which supports it are crucial to maintaining the existing large share of the international market for such vessels. Recently freight and military transport vessels have been exposed to much more severe wave conditions than passenger vessels and this has increased the need for improved prediction of structural loads due to waves. This project directly addresses that need by computation and model testing validation. The industry is a significant export earner and employer within Australia and so the project directly underpins those national benefits. Read moreRead less
Asymmetric and nonlinear unsteady loads on high speed ferries. Large high speed catamarans are expanding their domain of application from coastal passenger routes to ocean freight and military service. This is shifting operability criteria from motions and passenger discomfort to structural load limitations in severe wave environments. This project investigates large wave structural load prediction. Large waves lead to strongly non-linear responses, invalidating many methods of analysis. Predict ....Asymmetric and nonlinear unsteady loads on high speed ferries. Large high speed catamarans are expanding their domain of application from coastal passenger routes to ocean freight and military service. This is shifting operability criteria from motions and passenger discomfort to structural load limitations in severe wave environments. This project investigates large wave structural load prediction. Large waves lead to strongly non-linear responses, invalidating many methods of analysis. Prediction of loads on the transverse structure is also not possible with many prediction methods. This project will develop and validate by experiment fully time domain computational methods for the prediction of asymmetric structural loads due to large wavesRead moreRead less
A hybrid approach to predict the structure-borne noise transmission in ship structures using a waveguide method and Statistical Energy Analysis. The prediction of structure-borne noise transmission in large welded ship structures is required, in order to design maritime vessels with greater ship power and reduced weight, without increasing the noise levels. The aim of this project is to develop a hybrid approach for structural dynamic analyses using an analytical waveguide method and Statistical ....A hybrid approach to predict the structure-borne noise transmission in ship structures using a waveguide method and Statistical Energy Analysis. The prediction of structure-borne noise transmission in large welded ship structures is required, in order to design maritime vessels with greater ship power and reduced weight, without increasing the noise levels. The aim of this project is to develop a hybrid approach for structural dynamic analyses using an analytical waveguide method and Statistical Energy Analysis. The theoretical estimation and associated experimental measurement of the SEA parameters (modal density, coupling and internal loss factors) form the basis for the hybrid approach. The outcomes will result in improved predictive techniques for dynamic analyses of large complex resonant structures.Read moreRead less