Avian Influenza: Molecular Basis Of Potential Resistance To Neuraminidase Inhibitors
Funder
National Health and Medical Research Council
Funding Amount
$87,250.00
Summary
In this project we will visualize an avian flu protein bound to various antiviral drugs that are currently in the clinic (Relenza and Tamiflu) or are in clinical development. In the immediate term, the images derived from the project will be a valuable predictive tool for evaluating the likely effectiveness of antiviral drugs and vaccines in response to emerging viral resistance. In the longer term the images could be used to guide the development of new antivirals and vaccines against avian flu ....In this project we will visualize an avian flu protein bound to various antiviral drugs that are currently in the clinic (Relenza and Tamiflu) or are in clinical development. In the immediate term, the images derived from the project will be a valuable predictive tool for evaluating the likely effectiveness of antiviral drugs and vaccines in response to emerging viral resistance. In the longer term the images could be used to guide the development of new antivirals and vaccines against avian flu. This initiative brings together Industry leaders in the development of influenza antivirals and vaccines, CSL and Biota, with a leading Medical Research Institute.Read moreRead less
Assessment Of Interventions For Controlling Pandemic Influenza And Determining Data Needs To Inform These Assessments
Funder
National Health and Medical Research Council
Funding Amount
$183,040.00
Summary
The aim of this study is to help us prepare for a pandemic of influenza by comparing how effective the various available control strategies are at reducing transmission of the disease. The available control interventions include: reducing the number of close contacts we make with others, isolating cases after they are diagnosed, closing schools, quarantining households, quarantining individuals who are known to have been exposed to a case, and using antiviral drugs treat and protect people at ri ....The aim of this study is to help us prepare for a pandemic of influenza by comparing how effective the various available control strategies are at reducing transmission of the disease. The available control interventions include: reducing the number of close contacts we make with others, isolating cases after they are diagnosed, closing schools, quarantining households, quarantining individuals who are known to have been exposed to a case, and using antiviral drugs treat and protect people at risk of being infected. We will compare these control measures by taking due account of the ability and resources available for these interventions, and with regard to the need to maintain essential services. The comparisons will be made using mathematical models that describe the transmission of the infection. All available data and advice from experts will be used to ensure that realistic models are used for the comparisons. We will also use the models to determine the best use of the limited antiviral drugs available, until a vaccine becomes available. We will consider how the control strategy should be changed if a strain develops that is resistant to the antiviral drugs. In addition, we will determine what data need to be collected during the early stages of a pandemic to help us to determine the best use of the antiviral drugs, the best use of a new vaccine and to check on the development of resistance to the antiviral drugs.Read moreRead less
Rapid Point Of Care Detection Of Avian Influenza Virus Using Ion-Channel Switch Biosensor
Funder
National Health and Medical Research Council
Funding Amount
$425,400.00
Summary
The project aims to demonstrate a rapid, Point-of-Care test based on the Ion Channel Switch (ICS_) Biosensor for the detection and identification of Avian Influenza (AI) Virus in respiratory specimens. This proposal combines the extensive scientific skills and experience of the Institute of Medical and Veterinary Science (IMVS), Adelaide with the experience and existing capability of Ambri Ltd, Chatswood Sydney, to adapt an existing ICS_ Biosensor for the detection of avian influenza virus in cl ....The project aims to demonstrate a rapid, Point-of-Care test based on the Ion Channel Switch (ICS_) Biosensor for the detection and identification of Avian Influenza (AI) Virus in respiratory specimens. This proposal combines the extensive scientific skills and experience of the Institute of Medical and Veterinary Science (IMVS), Adelaide with the experience and existing capability of Ambri Ltd, Chatswood Sydney, to adapt an existing ICS_ Biosensor for the detection of avian influenza virus in clinical specimens. The existing ICS_ Biosensor has been shown to have reactivity with inactivated Influenza A (H1N1 and H3N2 _ current, circulating human strains) and with recombinant Nucleoprotein. This unique mix of experience and infrastructure will permit the demonstration a rapid, point-of-care test for Avian Flu within the tight six months schedule.Read moreRead less
Modelling The Biology And Transmission Of Influenza Virus - Learning From 1918-19 And Other Outbreaks
Funder
National Health and Medical Research Council
Funding Amount
$114,222.00
Summary
In preparing for a future pandemic of influenza, it is important to learn as much as possible from what happened in the past, particularly from the devastating pandemic of 1918-19. This project will collate detailed information about the spread of influenza in past outbreaks and create a publicly accessible data-base. Mathematical methods will be used to analyse historic and contemporary data, so as to provide better understanding of the spread of influenza, and of the likely effects of social a ....In preparing for a future pandemic of influenza, it is important to learn as much as possible from what happened in the past, particularly from the devastating pandemic of 1918-19. This project will collate detailed information about the spread of influenza in past outbreaks and create a publicly accessible data-base. Mathematical methods will be used to analyse historic and contemporary data, so as to provide better understanding of the spread of influenza, and of the likely effects of social and medical measures for its control. An important theme of the project is to consolidate our knowledge about how past exposure to non-pandemic influenza could provide short-lived protection against any new pandemic, and to explore the implications of this for prevention today. Another theme is to explore the severity of influenza during pandemics, and to identify social and medical factors that might reduce the dose of virus transmitted, or otherwise reduce the severity of infection. The insights from the modeling will also help to identify gaps in knowledge and understanding about the basic biology of influenza, stimulate new research to fill those gaps, and thus offer the prospect of more effective vaccines and treatments for the future control of influenza.Read moreRead less
Assessment Of Alpha-galactosylceramide As A Novel Adjuvant For Pandemic Influenza: A Virua Vaccine
Funder
National Health and Medical Research Council
Funding Amount
$220,042.00
Summary
The occurrence of human infections with pathogenic avian H5N1 Influenza A viruses was the first documentation of these viruses demonstrating an ability to directly transmit from birds to humans. The virulent nature of these infections, and the fact that there is no pre-existing immunity to these viruses in the human population has raised the concern that these viruses may emerge to cause the next influenza pandemic. Vaccination is our most effective way of protecting against influenza infection, ....The occurrence of human infections with pathogenic avian H5N1 Influenza A viruses was the first documentation of these viruses demonstrating an ability to directly transmit from birds to humans. The virulent nature of these infections, and the fact that there is no pre-existing immunity to these viruses in the human population has raised the concern that these viruses may emerge to cause the next influenza pandemic. Vaccination is our most effective way of protecting against influenza infection, however there are no commercially available avian influenza vaccines available. Moreover, recent evidence suggests current vaccines strategies may be less than effective. This proposal aims to evaluate the efficacy of a novel vaccine strategy that promotes immune protection against a potential pandemic influenza strain.Read moreRead less
Enterovirus 71 In The Asia-Pacific Region: Reverse Genetic Approaches To Virus Surveillance And Vaccine Development.
Funder
National Health and Medical Research Council
Funding Amount
$690,833.00
Summary
In this research the team will use advanced biotechnological techniques to study the distribution and virulence markers of an important emerging infectious disease, enterovirus 71 encephalitis, in the Asia-Pacific region. The knowledge and technical advances derived from this study will be shared with neighbouring countries in order to conduct sensitive surveillance for this infection throughout the region. The study's other major aim is to use cutting-edge biotechnological techniques to develop ....In this research the team will use advanced biotechnological techniques to study the distribution and virulence markers of an important emerging infectious disease, enterovirus 71 encephalitis, in the Asia-Pacific region. The knowledge and technical advances derived from this study will be shared with neighbouring countries in order to conduct sensitive surveillance for this infection throughout the region. The study's other major aim is to use cutting-edge biotechnological techniques to develop a genetically defined, live attenuated vaccine strain. Candidate vaccine strains will be tested for their effectiveness in both cell culture-based and animal models.Read moreRead less
Approaches to combat AIDS and its causative agent, the human immunodeficiency virus HIV-1, have thus far proved ineffective. The proposed research program intends to investigate the nuclear import of two HIV-1 proteins which have central roles in HIV infection. We will apply our expertise in the area of the regulation of nuclear import of viral proteins, and build on our observations with respect to these proteins to attempt to establish the mechanistic basis of their nuclear import, and how thi ....Approaches to combat AIDS and its causative agent, the human immunodeficiency virus HIV-1, have thus far proved ineffective. The proposed research program intends to investigate the nuclear import of two HIV-1 proteins which have central roles in HIV infection. We will apply our expertise in the area of the regulation of nuclear import of viral proteins, and build on our observations with respect to these proteins to attempt to establish the mechanistic basis of their nuclear import, and how this differs from the conventional nuclear import pathways used by normal cellular proteins. We already have evidence that nuclear import of HIV-Tat is regulated in novel fashion by cellular factors, and intend, through determining its mechanistic basis, to be able to form the basis of a strategy to block this import pathway specifically, and thereby inhibit HIV replication. This may form the basis in the future of a new pharmaceutical approach to combat HIV-AIDS.Read moreRead less
HIV infection of CD4+ lymphocytes leads to a high rate of reproduction of new virus. However, in the brain, HIV infection of the astrocytes does not yield high levels of new virus. HIV is genetically active in these astrocytes, producing high levels of the messenger molecules, the so-called mRNA, that code for the proteins required for a new virus particle. We have determined that these HIV mRNAs are specifically prevented from translating into protein. The mechanisms controlling protein transla ....HIV infection of CD4+ lymphocytes leads to a high rate of reproduction of new virus. However, in the brain, HIV infection of the astrocytes does not yield high levels of new virus. HIV is genetically active in these astrocytes, producing high levels of the messenger molecules, the so-called mRNA, that code for the proteins required for a new virus particle. We have determined that these HIV mRNAs are specifically prevented from translating into protein. The mechanisms controlling protein translation from RNA are relatively poorly understood compared with the other control points of cellular gene expression, such as the synthesis of mRNA. This project examines how astrocytes rapidly detect the presence of HIV mRNA and alter their translation machinery to halt the expression of HIV protein. This host defence mechanism involves two key components; the cellular component that identifies and responds to the viral mRNA, and the structural features of the HIV mRNA that enable the cell to detect its viral origin. We will study how translation of HIV proteins requires both HIV and cellular factors. We will determine the impact of both viral RNA elements and viral RNA binding proteins on the translation of viral and cellular proteins. The contribution of the type-1 interferons that are produced in response to viral infection will be studied for their role in augmenting the inhibition of HIV protein translation. Since HIV infected astrocytes significantly contribute to the onset of AIDS dementia, we will sees a strategy to lock HIV into a dormant state in the brain and thereby prevent the neurodegenerative disease associated with HIV. We will use the anti-viral mechanism blocking HIV protein translation in astrocytes to protect other cell populations, such as the CD4+ lymphocytes, from HIV infection. These studies will also give insights into the general mechanisms for translational control of gene expression in human cells.Read moreRead less