Sensitive, Rapid And Accurate Detection Of The Emergence Of Neuraminidase Inhibitor Resistance By Real-time PCR, LCR And
Funder
National Health and Medical Research Council
Funding Amount
$118,875.00
Summary
An influenza pandemic causing by highly pathogenic H5N1 virus may occur in the near future. As a vaccine for H5N1 will not be available in the foreseeable months, antiviral drugs are the only possible choice for prophylaxis and treatment. Currently only two drugs have been clinically proven to be effective against H5N1 strain and the emergence of drug resistant in H5N1 influenza virus has been reported which may significantly hamper the treatment. Understanding and monitoring the emergence of th ....An influenza pandemic causing by highly pathogenic H5N1 virus may occur in the near future. As a vaccine for H5N1 will not be available in the foreseeable months, antiviral drugs are the only possible choice for prophylaxis and treatment. Currently only two drugs have been clinically proven to be effective against H5N1 strain and the emergence of drug resistant in H5N1 influenza virus has been reported which may significantly hamper the treatment. Understanding and monitoring the emergence of these drug resistant strains during local spreading will be critical in managing an H5N1 influenza pandemic in Australia. In the proposed project, we will develop important diagnostic tools using our world leading Rolling Circle Amplification (RCA) technology for the monitoring of the development and possible transmission of drug resistant influenza strains. Upon finishing the project, at lease three sensitive diagnostic methods will be developed for the detection of the emergence of drug resistance at the very early stage.Read moreRead less
Strenthening The Contribution Of Australian General Practice To The Control Of Pandemic Influenza
Funder
National Health and Medical Research Council
Funding Amount
$110,257.00
Summary
Most primary and preventive care in Australia occurs in general practice. Australian general practice will therefore have a critical role to play in control efforts during an influenza pandemic, and also in sustaining other primary health care activities. After an initial surge in attendances, there may be a decline in attendance, as Australians become more reluctant to congregate in a place where they may become ill. This study seeks to complement the Australian Pandemic Influenza Management Pl ....Most primary and preventive care in Australia occurs in general practice. Australian general practice will therefore have a critical role to play in control efforts during an influenza pandemic, and also in sustaining other primary health care activities. After an initial surge in attendances, there may be a decline in attendance, as Australians become more reluctant to congregate in a place where they may become ill. This study seeks to complement the Australian Pandemic Influenza Management Plan by developing a range of action plans for use by general practitioners and public health authorities to support essential primary health care functions through a pandemic, and maximize general practice's contribution to control efforts. A range of methods will be used, including systematic review of existing literature, economic modeling of the Medicare costs and savings of different models of health care, interviews with key informants who have helped develop disaster response plans for general practice, or who are in positions of leadership. The project will culminate in the development of a simulation exercise to be used as a self-assessment tool for general practitioners, and a summit of general practice stakeholders who will help to finalise agreed action plans for the general practice response to pandemic influenza.Read moreRead less
Establishing The Capacity For H5N1 Challenge Of Ferrets Within Australia &optimizing Pandemic Vaccines In This Model
Funder
National Health and Medical Research Council
Funding Amount
$405,513.00
Summary
Australia is currently in the process of manufacturing vaccines for use in people against strains of avian influenza viruses circulating in South East Asia as part of a national preparedness program for an influenza pandemic. These particular avian flu viruses are capable of causing severe disease and death in humans as well as birds, although at present they are not highly transmissible between people. Should the avian influenza viruses mutate to gain this capability, it will be necessary to in ....Australia is currently in the process of manufacturing vaccines for use in people against strains of avian influenza viruses circulating in South East Asia as part of a national preparedness program for an influenza pandemic. These particular avian flu viruses are capable of causing severe disease and death in humans as well as birds, although at present they are not highly transmissible between people. Should the avian influenza viruses mutate to gain this capability, it will be necessary to institute widespread vaccination of the Australian population. It is not possible to test the vaccines in people for their effectiveness against avian influenza infection prior to a disease outbreak, so an animal model for the disease will be used to assist in optimizing the formulation of flu vaccines and in testing their efficacy in preventing infection or reducing the severity of disease. Ferrets are natural hosts for flu viruses, have similar responses to vaccination as people, and develop a similar disease to humans when infected with influenza. These animals will be used to assist vaccine manufacturers in providing the best type of vaccine for protection of Australians in the face of a global flu pandemic.Read moreRead less
Screening Agents Active Against The Late-stage Inflammatory Cytokines For Activity Against Influenza Disease
Funder
National Health and Medical Research Council
Funding Amount
$241,409.00
Summary
Infection with a virulent influenza virus that the body has never encountered before, particularly H5N1, sends the immune system into overdrive, and causes a massive release of proteins (inflammatory cytokines), known as a cytokine storm, that in and of itself leads to death. The object of this research is to screen, in a mouse influenza model, agents known to prevent this occurring and antagonise it once it has occurred. This will be done with and without Tamiflu, a standard anti-influenza drug ....Infection with a virulent influenza virus that the body has never encountered before, particularly H5N1, sends the immune system into overdrive, and causes a massive release of proteins (inflammatory cytokines), known as a cytokine storm, that in and of itself leads to death. The object of this research is to screen, in a mouse influenza model, agents known to prevent this occurring and antagonise it once it has occurred. This will be done with and without Tamiflu, a standard anti-influenza drug.Read moreRead less
Enhancing Australia's Pandemic Influenza Vaccine Output By Increasing The Yeild Of Vaccine From Eggs
Funder
National Health and Medical Research Council
Funding Amount
$251,517.00
Summary
Influenza epidemics cause significant morbidity and mortality, particularly amongst the young and elderly. Unlike other vaccines, a new flu vaccine formulation needs to be prepared each year from the currently circulating strain. This involves a long process of preparing new seed vaccine stock, which is then tested, manufactured and distributed. The situation is even more complicated by the ability of different influenza strains to reassort with others. An example of current major concern is the ....Influenza epidemics cause significant morbidity and mortality, particularly amongst the young and elderly. Unlike other vaccines, a new flu vaccine formulation needs to be prepared each year from the currently circulating strain. This involves a long process of preparing new seed vaccine stock, which is then tested, manufactured and distributed. The situation is even more complicated by the ability of different influenza strains to reassort with others. An example of current major concern is the possibility of deadly avian flu viruses, such as H5N1, to gain the capacity to directly infect humans by recombining with a human strain and thereby starting a new global pandemic. When the next influenza pandemic occurs, the availability of a vaccine will be of the highest priority and early supply of vaccines will save millions of lives. Since vaccination is the only sustainable defense, we face an urgent need to have the capacity to supply large numbers of vaccine doses of influenza vaccines within a short period of time. Currently, the only way of producing flu vaccines is in eggs. The speed of vaccine supply is totally dependant on the yield of vaccine from eggs and the number of eggs that can be processed at any one time. Since there are severe constraints on the number of eggs that can be simultaneously processed, the limiting factor that can be addressed is the actual yield of vaccine per egg. The aim of this project is the develop methods that allow higher levels of vaccine virus to grow in eggs. We will take a multi-pronged approach to enhancing influenza vaccine production that are directed toward increasing the capacity of eggs to promote virus replication, as well as towards the vaccine strain to boost its ability to replicate in the egg. The outcome will be an enhanced capacity for vaccine manufacturers to quickly and effectively expand vaccine supplies which will directly impact on global morbidity and mortality during a flu pandemic.Read moreRead less
Self Adjuvanting CTL-Based Influenza Vaccines For Human Use
Funder
National Health and Medical Research Council
Funding Amount
$214,842.00
Summary
This project will generate novel vaccines that elicit cell-mediated immunity against influenza infection. The vaccines are totally synthetic and therefore not constrained by the limitations in manufacturing which currently confront egg-grown vaccines. These vaccines induce very strong immune responses because they target dendritic cells which are pivotal for induction of all immune responses. This targeting capability is due to a simple lipid molecule incorporated into the vaccine which is recog ....This project will generate novel vaccines that elicit cell-mediated immunity against influenza infection. The vaccines are totally synthetic and therefore not constrained by the limitations in manufacturing which currently confront egg-grown vaccines. These vaccines induce very strong immune responses because they target dendritic cells which are pivotal for induction of all immune responses. This targeting capability is due to a simple lipid molecule incorporated into the vaccine which is recognised by specific receptors on the surface of dendritic cells and also causes their maturation, a step which is essential for recognition by the immune system of potential pathogens. The technology to design and assemble these new vaccines is already.Read moreRead less
Gamma-ray Inactivated Influenza A Virus Vaccine For Cross-protective T Cell Immunity
Funder
National Health and Medical Research Council
Funding Amount
$239,963.00
Summary
Although there are new antiviral drugs that appear to be effective against influenza virus, the far more costeffective and efficient means to combat an influenza pandemic would be by vaccination. Current influenza vaccines employ virus preparations that are inactivated by chemical treatment. The inactivated vaccines, which function mostly by inducing antibody against the virus, have to be reformulated almost every year to take account of the changing virus because the antibodies recognize the vi ....Although there are new antiviral drugs that appear to be effective against influenza virus, the far more costeffective and efficient means to combat an influenza pandemic would be by vaccination. Current influenza vaccines employ virus preparations that are inactivated by chemical treatment. The inactivated vaccines, which function mostly by inducing antibody against the virus, have to be reformulated almost every year to take account of the changing virus because the antibodies recognize the viral surface which is prone to mutation. Accordingly, in terms of the threatening H5N1 avian influenza pandemic, it is not known if an inactivated vaccine based on the circulating H5N1 strain will be effective if the virus mutates to adapt to efficient growth and spread in the human population. In contrast to the antibody response against influenza virus, the cytotoxic T cell response is broadly crossreactive between heterologous influenza virus strains. Live virus infection efficiently induces cytotoxic T cell immunity which plays an important role in reducing disease severity and mortality following infection with a second, heterologous influenza virus, although infection per se is not prevented. Accordingly, vaccination strategies that elicit cytotoxic T cell memory should be given urgent consideration in the preparation against an influenza pandemic. We have found that the use of gamma-irradiation (in contrast to chemical treatment) for the preparation of inactivated experimental vaccines against influenza and other viruses does not destroy the ability of the vaccines to elicit cytotoxic T cell immunity. The gamma-ray inactivated vaccines conferred protection against lethal challenge with heterologous influenza virus strains in mice. This proposal is aimed at extending this novel finding to avian influenza viruses and to uncover the mechanisms involved in the cytotoxic T cell immunogenicity of gamma-ray inactivated vaccines.Read moreRead less
Neonatal Immunization With Pneumococcal Conjugate Vaccine In Papua New Guinea
Funder
National Health and Medical Research Council
Funding Amount
$1,181,966.00
Summary
One million children die every year of pneumococcal (Pnc) disease, the majority in the third world. Many die in early infancy and babies may benefit from immunisation with a Pnc conjugate vaccine (PrevenarTM) at birth. The Papua New Guinea (PNG) Insatiate of Medical Research; Telethon Institute for Child Health Research and the Department of Paediatrics, University of Western Australia, will collaborate to closely examine the safety of this approach, particularly with regard to impact on the dev ....One million children die every year of pneumococcal (Pnc) disease, the majority in the third world. Many die in early infancy and babies may benefit from immunisation with a Pnc conjugate vaccine (PrevenarTM) at birth. The Papua New Guinea (PNG) Insatiate of Medical Research; Telethon Institute for Child Health Research and the Department of Paediatrics, University of Western Australia, will collaborate to closely examine the safety of this approach, particularly with regard to impact on the development of immunity and response to other vaccines given to infants. This study will also provide a unique opportunity for training of PNG and Australian scientists in both countries; transfer state-of-the-art immunological technology and stimulate further collaborations on respiratory infections in the region.Read moreRead less