Optimising Immunity Towards Cancers By Vaccination.
Funder
National Health and Medical Research Council
Funding Amount
$211,320.00
Summary
In this project we will be studying the mechanisms of how an efficient anti cancer vaccine could be generated. We will be using cervical cancer associated human papillomavirus type 16 E7 protein as the model protein in an experimental vaccine model in mice. The results obtained from this project not only able us to design better vaccines against cervical cancers in women but against many other cancers and viruses.
Malaria infects millions of people worldwide causing serious morbidity and mortality. However, individuals do not develop natural immunity to malaria even after years of exposure to the parasite. There have be a multitude of attempts to make a vaccine , with products going to clinical trials, but no vaccine is able to provide adequate protection for the long term. We recently showed that Plasmodium had evolved a mechanism to kill cells that protect in the long-term. This study will investigate t ....Malaria infects millions of people worldwide causing serious morbidity and mortality. However, individuals do not develop natural immunity to malaria even after years of exposure to the parasite. There have be a multitude of attempts to make a vaccine , with products going to clinical trials, but no vaccine is able to provide adequate protection for the long term. We recently showed that Plasmodium had evolved a mechanism to kill cells that protect in the long-term. This study will investigate the mechanism by which the parasite kill these cells, so that novel therapies can be designed.Read moreRead less
In recent years it has become clear that certain white blood cells called CD8+ T lymphocytes or killer T cells are required to protect people against HIV. Unfortunately, current vaccines that produce or anti-HIV CD8 T cells only produce effective T cells for a short period. In this project we intend to test a novel vaccine vector called a Kunjin replicon, which promises to persistently produce or maintain effective T cells because the vaccine itself persists and continually immunises for extende ....In recent years it has become clear that certain white blood cells called CD8+ T lymphocytes or killer T cells are required to protect people against HIV. Unfortunately, current vaccines that produce or anti-HIV CD8 T cells only produce effective T cells for a short period. In this project we intend to test a novel vaccine vector called a Kunjin replicon, which promises to persistently produce or maintain effective T cells because the vaccine itself persists and continually immunises for extended periods. We intend to test the ability of this vaccine to persist and persistently produce effective CD8 T cells not only systemically in the blood system but also at mucosal surfaces, where HIV usually gains entry during sexual intercourse.Read moreRead less
Impact Of Influenza A Infection On T Cell-mediated Immunity To Pulmonary Tuberculosis.
Funder
National Health and Medical Research Council
Funding Amount
$488,058.00
Summary
Tuberculosis is a leading cause of death worldwide and there is an urgent need to develop better anti-TB vaccines. Infection with respiratory viruses may reduce memory T cell responses to M. tuberculosis (Mtb). This project will investigate if Influenza A infection reduces memory anti-tuberculosis T cell responses in mice previously exposed to Mtb or BCG. We will then use influenza viruses engineered to carry parts of Mtb proteins to boost anti-Mtb T cell responses and the protective effect of B ....Tuberculosis is a leading cause of death worldwide and there is an urgent need to develop better anti-TB vaccines. Infection with respiratory viruses may reduce memory T cell responses to M. tuberculosis (Mtb). This project will investigate if Influenza A infection reduces memory anti-tuberculosis T cell responses in mice previously exposed to Mtb or BCG. We will then use influenza viruses engineered to carry parts of Mtb proteins to boost anti-Mtb T cell responses and the protective effect of BCG.Read moreRead less
Development Of Improved Vaccine Strategies For Measles Using Plant-derived Edible Vaccines
Funder
National Health and Medical Research Council
Funding Amount
$331,980.00
Summary
Measles is a highly contagious viral disease that is contracted via the respiratory tract. Severe infection may lead to complications such as otitis media, pneumonia, encephalitis. Despite our current vaccination strategy outbreaks still occur in Australia and measles is a major problem in developing countries. In developing nations the case fatality rate of measles is several hundred times that of developed nations. Over 800,000 children still die each year due to measles. Problems with the cur ....Measles is a highly contagious viral disease that is contracted via the respiratory tract. Severe infection may lead to complications such as otitis media, pneumonia, encephalitis. Despite our current vaccination strategy outbreaks still occur in Australia and measles is a major problem in developing countries. In developing nations the case fatality rate of measles is several hundred times that of developed nations. Over 800,000 children still die each year due to measles. Problems with the current vaccination strategy are: a) doesn't work in children less than 1 year of age, b) must be kept cold c) must be given by injection. We believe that a plant derived edible vaccine for measles will address the limitations of currently available vaccine i.e. we can give it children under the age of 1 year, it can be eaten and doesn't have to be kept cold.Read moreRead less
Kunjin Virus Replicon-based Vaccine Vectors: New Developments And Applications
Funder
National Health and Medical Research Council
Funding Amount
$227,036.00
Summary
The project is aimed towards further development of a unique gene expression and delivery system based on self-replicating RNA (replicon) of the nonvirulent Australian flavivirus Kunjin (KUN). A number of improvements in the design of KUN replicon vectors aimed to increase their efficiency and to optimize them for production of heterologous gene products with desired terminal sequences are proposed. Also proposed are improvements in the current KUN replicon packaging system and development of ne ....The project is aimed towards further development of a unique gene expression and delivery system based on self-replicating RNA (replicon) of the nonvirulent Australian flavivirus Kunjin (KUN). A number of improvements in the design of KUN replicon vectors aimed to increase their efficiency and to optimize them for production of heterologous gene products with desired terminal sequences are proposed. Also proposed are improvements in the current KUN replicon packaging system and development of new packaging systems for production of large amounts of virus-like particles (VLPs) containing KUN replicon RNA enclosed in KUN coat proteins for use as potential vaccines. The vaccine potentials of the curent and newly developed KUN vectors and VLPs will be evaluated in mice using respiratory syncytial virus as a model. An entirely new direction proposed in this application is generation of chimeric fowlpox virus-KUN replicon vectors which will combine the advantages of both systems and may result in the generation of an ultimate vaccine vector.Read moreRead less
RV3 Rotavirus Vaccine: A Human Neonatal Rotavirus Vaccine For The Asia-Pacific Region
Funder
National Health and Medical Research Council
Funding Amount
$2,264,330.00
Summary
Rotavirus infection is the leading cause of severe dehydrating gastroenteritis responsible for ~600,000 deaths per year in children <5 years of age worldwide. In this proposal we outline plans for the development of a human neonatal rotavirus vaccine in Indonesia. The goal is a safe and effective rotavirus vaccine affordable for children within the Asia-Pacific region and worldwide.
Molecular Approaches To Developing Subunit Vaccines With Improved Efficacy Against Tuberculosis
Funder
National Health and Medical Research Council
Funding Amount
$480,750.00
Summary
Tuberculosis remains a major worldwide health problem, resulting in approximately 3 million deaths per year. Furthermore, people infected with the AIDS virus are at a much greater risk of catching tuberculosis. The only vaccine available for tuberculosis, known as BCG, is not very effective at preventing the disease. Therefore there is an urgent need to develop new vaccines to help combat tuberculosis. The bacterium that causes tuberculosis is made up of may proteins, some of which are known to ....Tuberculosis remains a major worldwide health problem, resulting in approximately 3 million deaths per year. Furthermore, people infected with the AIDS virus are at a much greater risk of catching tuberculosis. The only vaccine available for tuberculosis, known as BCG, is not very effective at preventing the disease. Therefore there is an urgent need to develop new vaccines to help combat tuberculosis. The bacterium that causes tuberculosis is made up of may proteins, some of which are known to induce immune responses in animals and humans. We will produce vaccines that are made from 13 of these important proteins. Using a laboratory animal model that closely mimics human tuberculosis infection, together with sophisticated immunological techniques, we will determine if these vaccines stimulate the right immune response to fight tuberculosis and prevent infection. In addition, we will exploit molecules known to boost immune responses to optimise these vaccines. Further we will study the recently sequenced genome of the tuberculosis bacterium to identify new proteins that may be included in these novel anti-tuberculosis vaccines. This is an internationally competitive project and our team is at the forefront of this research effort. A new, effective tuberculosis vaccine would be a major medical breakthrough and a represent a significant achievement for Australian health and medical research.Read moreRead less
Characterisation Of HiaNm, A Novel Outer Membrane From Neisseria Meningitidis; Vaccine Potential And Functional Studies
Funder
National Health and Medical Research Council
Funding Amount
$356,685.00
Summary
Meningococcal meningitis is a devastating illness which mostly affects children under 5 years. The clinical presentation is of a rapidly progressing disease with high rates of morbidity and mortality. This disease is caused by a bacterium, Neisseria meningitidis (the meningococcus). Vaccines are available against serogroup A and C strains of N. meningitidis, but not for group B strains, which cause the majority of disease in industrialised countries. We have recently identified a gene (designate ....Meningococcal meningitis is a devastating illness which mostly affects children under 5 years. The clinical presentation is of a rapidly progressing disease with high rates of morbidity and mortality. This disease is caused by a bacterium, Neisseria meningitidis (the meningococcus). Vaccines are available against serogroup A and C strains of N. meningitidis, but not for group B strains, which cause the majority of disease in industrialised countries. We have recently identified a gene (designated hiaNm) which encodes a new protein which is located on the surface of the bacterium, in the outer membrane. There has been an enormous body of work done on the immunology, biochemistry and genetics of all components of the outer membrane of Neisseria meningitidis. Therefore the discovery of this novel protein provides an exciting opportunity to take a new direction in vaccine development. For an effective vaccine, the target molecule must be present in most strains; we have already shown that the hiaNm gene is present in all strains examined. In this proposal we describe a study of the vaccine potential and biological function of the hiaNm gene product HiaNm. We will express the protein at high levels, immunise mice, and produce antibodies against HiaNm to discover whether they can protect mice against meningococcal disease. At the completion of this set of experiments we will be in an excellent position to assess the potential for the further development of HiaNm as a component of a meningococcal vaccine.Read moreRead less