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
Evaluation And Comparison Of Lentiviral And AAV Vector Mediated Gene Therapy For The Mucopolysaccharidoses
Funder
National Health and Medical Research Council
Funding Amount
$521,320.00
Summary
The mucopolysaccharidoses are a group of inherited diseases that have profound consequences for affected individuals. They have pleiotropic effects and usually result in premature death. Although intravenous enzyme replacement therapy has been developed for a number of these disorders, this approach to therapy is invasive, very expensive, of limited efficacy, and is completely ineffective in treating brain pathology. The principal reason for this is the protected nature of the brain which preven ....The mucopolysaccharidoses are a group of inherited diseases that have profound consequences for affected individuals. They have pleiotropic effects and usually result in premature death. Although intravenous enzyme replacement therapy has been developed for a number of these disorders, this approach to therapy is invasive, very expensive, of limited efficacy, and is completely ineffective in treating brain pathology. The principal reason for this is the protected nature of the brain which prevents enzymes that are administered intravenously from entering. Therefore, alternative therapies must be considered in order to provide more effective therapy for the mucopolysaccharidoses, especially those that have significant brain pathology. Gene therapy is one such alternative therapy but this still faces the problem of introducing the therapeutic agent (in this case the gene encoding the requisite enzyme) into the brain. This project aims to provide a comparitive evaluation of two gene therapy vectors for their efficacy in treating all aspects of the pathology found in the mucopolysaccharidoses. Both vectors have the properties of being able to efficiently deliver genes to different cell types and result in the stable genetic modification of the target cell, making them ideal for long-term treatment. However, for effective gene therapy, significant and widely distributed gene delivery to the brain, as well as to other tissues, will be required. This project aims to compare the efficacy of these vectors in two different animal models of the mucopolysaccharidoses that exhibit a wide range of the clinical problems associated with these diseases, importantly including brain pathology.Read moreRead less
Dengue is the leading mosquito-borne virus causing morbidity and mortality in the tropics. North Queens land has a history of dengue outbreaks, with 5 outbreaks in the last 3 years. Queensland Health has developed a Dengue Fever Management Plan for north Queensland that has had considerable success in preventing small outbreaks of dengue from developing into large epidemics. The cornerstone of this plan is the application of residual insecticide inside premises near dengue cases to kill the mosq ....Dengue is the leading mosquito-borne virus causing morbidity and mortality in the tropics. North Queens land has a history of dengue outbreaks, with 5 outbreaks in the last 3 years. Queensland Health has developed a Dengue Fever Management Plan for north Queensland that has had considerable success in preventing small outbreaks of dengue from developing into large epidemics. The cornerstone of this plan is the application of residual insecticide inside premises near dengue cases to kill the mosquito vector, Aedes aegypti, before it can spread the virus. While this method is effective, it is labor intensive, requires the cooperation of homeowners who may find it intrusive and exposes nontarget insects and animals to insecticide. We propose to develop a lure and kill strategy to improve the efficacy of vector control while minimising the exposure of nontarget animals. Several chemicals have been identified as highly attractive to dengue mosquitoes. Among these are extracts from water infusions of grass that are highly attractive to egg-laying mosquitoes and emanations from human skin that attract host-seeking mosquitoes. We will develop traps incorporating a. mosquito attractants and b. a killing agent to selectively control Ae. aegypti mosquitoes. These will be collectively called lethal traps. This project will employ the following approach towards the development of a lure and kill strtaegy for dengue control a. determine which compounds are most attractive to north Queensland Ae. aegypti in a laboratory wind tunnel; b. confirm the attraction of these compounds using sticky traps in the field; c. conduct field trials of candidate lethal traps to determine the spacing and density of traps needed to control mosquitoes d. conduct a large field trial to examine the efficacy of the optimised lure and kill strategy. We will also conduct ecological studies on aging and the flight range of Ae. aegypti to enhance the development of the strategy.Read moreRead less
Development Of Early Warning Systems For Dengue Fever Based On Socio-ecological Factors
Funder
National Health and Medical Research Council
Funding Amount
$327,402.00
Summary
Global climate change has potentially serious effects on the transmission of dengue. An early warning system (EWS) based on socio-ecological factors will be developed to examine where and when outbreaks of dengue are likely to occur and how the future dengue control strategies and prevention efforts need to be applied and strengthened in Australia. This project will provide a platform for future research on developing and implementing an EWS for dengue in the Asia-Pacific region.
Population Dynamics And Evolution Of Mosquitoes That Transmit Malaria
Funder
National Health and Medical Research Council
Funding Amount
$381,807.00
Summary
Population dynamics and evolutionary process are fundamental to mosquito-borne infectious diseases as evolutionary forces steer both mosquito and malaria parasite to evolve around obstacles in their natural development. Environmental and ecological factors also influence the relationship between mosquito, parasite and humans. Therefore control of mosquito borne disease depends on an innate understanding of the genetics, behavior and environment. Thus studies on mosquito population dynamics inclu ....Population dynamics and evolutionary process are fundamental to mosquito-borne infectious diseases as evolutionary forces steer both mosquito and malaria parasite to evolve around obstacles in their natural development. Environmental and ecological factors also influence the relationship between mosquito, parasite and humans. Therefore control of mosquito borne disease depends on an innate understanding of the genetics, behavior and environment. Thus studies on mosquito population dynamics including population densities, migration, population subdivisions and competition for resources will allow an understanding of these relationships. Island populations of malaria transmitting mosquitoes contain less genetic complexity (genetic variation in mosquito subpopulations) than mainland populations. Thus mosquito island populations may not contain the genetic capability of evolving around detrimental selection pressures such as the use of insecticides or predators. Armed with accurate knowledge of genetic complexity, biology and behavior of mosquito disease vector species, control measures can be accurately focused at specific populations (high disease transmission mosquito populations). This project we will identify specific populations of mosquitoes using their DNA to reveal genetic markers for specific behavior traits. Due to the smaller amount of genetic variations that island mosquito populations contain, and our aquired knowledge of their behavior and biology. We will design focused mosquito control strategies with knowledge that the mosquitoes will have a smaller chance of evolving around these control measures.Read moreRead less
Can Lure And Kill Strategies Prevent Dengue Transmission In North Queensland, Australia
Funder
National Health and Medical Research Council
Funding Amount
$318,621.00
Summary
Dengue fever is a growing threat to human health in the tropics. In north Queensland, 11 dengue outbreaks have resulted in 985 confirmed cases since 2000. Furthermore, 2004 saw the emergence of severe disease, with 4 cases of dengue haemorrhagic fever resulting in at least one death in the Torres Strait. The current dengue managment plan employs methods to control larvae and adults of the mosquito vector, Aedes aegypti. Adult control consists of spraying dark, protected areas inside houses and b ....Dengue fever is a growing threat to human health in the tropics. In north Queensland, 11 dengue outbreaks have resulted in 985 confirmed cases since 2000. Furthermore, 2004 saw the emergence of severe disease, with 4 cases of dengue haemorrhagic fever resulting in at least one death in the Torres Strait. The current dengue managment plan employs methods to control larvae and adults of the mosquito vector, Aedes aegypti. Adult control consists of spraying dark, protected areas inside houses and buildings with a residual pyrethroid insectcide. However, this method is laborious and exposes residents and the environment to pesticide. Our research team, funded by NHMRC project grant no. 279401, has developed lure and kill methods to kill Ae. aegypti mosquitoes using traps. These traps are baited with chemicals that attract female dengue mosquitoes trying to bite (host-seeking traps; HSTs) or trying to lay eggs (lethal ovitraps; LOs). The use of traps to kill specific target insects is termed lure and kill strategy. This strategy reduces the amount of pesticide used by 1000X, and are twice as fast to employ than house spraying. We are seeking funding to conduct a series of field trials to provide proof of concept that the lure and kill strategy will rapidly reduce populations of Ae. aegypti and thus stop dengue transmission. These trials will be conducted in the Cairns area. We will also trial a biodegradable lethal ovitrap that could be put into yards without having to return to retrieve the trap. The trap would simply biodegrade after 4 weeks, and thus pose no threat to become a mosquito breeding site once the pesticide had become ineffective. A biodegradable trap would be especially useful in the Torres Strait where return visits are costly and time consuming. Finally, we propose to trial a new paper strip device that emits vapors of the pyrethriod insecticide metofluthrin, shown to repel mosquitoes for weeks, to set in dengue case houses.Read moreRead less