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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
Determination Of The Efficacy And Resistance Profile Of A Long Acting Neuraminidase Inhibitor Against Several Avian Infl
Funder
National Health and Medical Research Council
Funding Amount
$91,350.00
Summary
Recent events have again highlighted influenza�s potential to cause a worldwide pandemic or be used as an agent of biowarfare. As of August 2005, the highly pathogenic Avian Flu sweeping through Asia has infected 112 people, killing 57. Over 150 million chickens have been slaughtered in an attempt to stop its spread, but with infection documented in migratory birds, containment may be difficult if not impossible. Experts believe that it is only a matter of time before the Avian Flu virus is capa ....Recent events have again highlighted influenza�s potential to cause a worldwide pandemic or be used as an agent of biowarfare. As of August 2005, the highly pathogenic Avian Flu sweeping through Asia has infected 112 people, killing 57. Over 150 million chickens have been slaughtered in an attempt to stop its spread, but with infection documented in migratory birds, containment may be difficult if not impossible. Experts believe that it is only a matter of time before the Avian Flu virus is capable of human to human transmission which could result in the deaths of hundreds of thousands of people worldwide. Should a pandemic arise, either through purposely-engineered or natural processes such as avian influenza, effective vaccines are unlikely to be available for at least 3-6 months. In such an event, treatment of infection and prevention of spread through post-exposure prophylaxis would be optimal, while pre-exposure prophylaxis would be most suited to key personnel such as army, medical and emergency-response staff. Biota is a world leading antiviral drug discovery company based in Melbourne, Australia with key expertise in viral respiratory diseases, particularly influenza. Biota developed the first in class neuraminidase inhibitors (NAI) drug, zanamivir (Relenza) and through a partnership with Glaxo Smith Kline (GSK) brought it to market. Biota also developed the FluOIA� for the rapid detection of Influenza A and B. Work has been underway at Biota for some time to develop a new generation of influenza drugs designed to be more active and longer acting than the first generation products. These long acting neuraminidase inhibitors (LANI) have the benefit of less frequent administration and a lower treatment dose making them an ideal choice for stockpiling. The proposed project aims to test the antiviral activity of LANI compound against the H5N1 influenza. The results of which could assist in a decision to fast track the clinical development of the compound with the aim of adding to the national stock pile of antivirals, thus helping Australia to prevent, prepare for and respond to a potential avian influenza-induced pandemic.Read moreRead less
Mucosal Vaccine For Influenza On Inactivated Virus And Mannan
Funder
National Health and Medical Research Council
Funding Amount
$131,993.00
Summary
Influenza is a respiratory disease that causes significant morbidity and mortality worldwide. Current influenza vaccines are a preparation of three currently circulating inactivated influenza strains that induces an antibody response that can combat the virus and therefore infection. Despite the availability of a vaccine new approaches are needed to increase the activity, usage and distribution. To this end several approaches based on using additional agents to increase the immunogenicity and ne ....Influenza is a respiratory disease that causes significant morbidity and mortality worldwide. Current influenza vaccines are a preparation of three currently circulating inactivated influenza strains that induces an antibody response that can combat the virus and therefore infection. Despite the availability of a vaccine new approaches are needed to increase the activity, usage and distribution. To this end several approaches based on using additional agents to increase the immunogenicity and needle free delivery are being explored. We have a natural sugar based compound that can be used to increase the body's immunity to cancers and infectious agents such as bacteria and viruses. When these preparations are applied into the nostril of mice they generate antibody responses to the infectious agent in the lungs, gut, tears, saliva that can act as a barrier to infectious agents. We are incorporating an inactive flu virus with this natural sugar to investigate if it produces antibody that can protect mice and ferrets from the flu virus. This method will be first tried with the human flu virus and if successful will be tried with the bird flu virus. If the preparation can protect mice and ferrets from human or bird flu infection it could develop into a human vaccine against bird flu. Since it can be administered by the nose it will be widely used and can be used readily without qualified personnel in the case of a pandemic.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
Australia-Europe Malaria Research Cooperation - OzEMalaR
Funder
National Health and Medical Research Council
Funding Amount
$859,731.00
Summary
EVIMalaR is a European Virtual Institute for Malaria Research that combines 42 of the European Union’s leading malaria research groups plus 4 Africans, 1 Indian institution, and 1 Australian. EVIMalaR faculty will combine expertise to produce a Network of Excellence that enhances and harmonises experimental approaches through shared technological platforms, exchange visits, shared PhD students, shared resources such as databases, reagent banks and protocols across pathology, infection, immunolog ....EVIMalaR is a European Virtual Institute for Malaria Research that combines 42 of the European Union’s leading malaria research groups plus 4 Africans, 1 Indian institution, and 1 Australian. EVIMalaR faculty will combine expertise to produce a Network of Excellence that enhances and harmonises experimental approaches through shared technological platforms, exchange visits, shared PhD students, shared resources such as databases, reagent banks and protocols across pathology, infection, immunology and biochemistry. Malaria is a global problem with no single solution. A large, but sometimes disjointed, research community is addressing the problem, but more collaboration is vital. OzEMalaR will link 34 Australian labs with 47 European, African and Indian malaria researchers. Funding will enable exchange of modern technologies by supporting early career researchers (PhD and postdocs) from Australia to work and be trained in top European labs. European trainees will work and be trained by Australian malariologists using reciprocal EU supportRead moreRead less
Are Routine Healthcare Worker Hand Hygiene Protocols (soap/water, Alcohol-based Handrub) Effective Against Influenza?
Funder
National Health and Medical Research Council
Funding Amount
$99,950.00
Summary
Although influenza is mainly spread from person-to-person by aerosol transmission (coughing, sneezing etc), there is growing evidence that spread also occurs on the hands of infected patients and their carers (non-aerosol transmission). Because of this, health authorities now recommend the use of careful hand hygiene (HH: hand washing with soap-water or use of alcohol-based hand rub solutions [ABHRS]) by healthcare workers (HCWs) and patients. However, despite these recommendations, there are no ....Although influenza is mainly spread from person-to-person by aerosol transmission (coughing, sneezing etc), there is growing evidence that spread also occurs on the hands of infected patients and their carers (non-aerosol transmission). Because of this, health authorities now recommend the use of careful hand hygiene (HH: hand washing with soap-water or use of alcohol-based hand rub solutions [ABHRS]) by healthcare workers (HCWs) and patients. However, despite these recommendations, there are no data that demonstrate the effectiveness of such HH protocols. This project aims to assess the clinical effectiveness of four HH protocols (handwashing with soap-water, alcohol-only ABHRS, two alcohol-chlorhexidine ABHRS) in common use in Australian hospitals to see which protocol is best for killing influenza virus. We also plan to assess how long influenza virus remains infectious on HCWs hands if they fail to use appropriate HH. Since it could be dangerous to use live avian influenza virus in this study, we plan to use the H1N1 influenza A strain that was a component of the influenza vaccine administered to most HCWs in 2005. Thus, only HCWs with protective immunity to H1N1 will participate in a series of tests in which they will have their hands artificially contaminated with a known concentration of live H1N1 before using either no HH, or one of the four HH protocols, followed by an assessment (virus culture and molecular tests) or the amount of H1N1 surviving on their hands after each protocol. Some selected HCWs will also have the amount of surviving virus assessed 30 and 60 minutes after contamination to identify how long H1N1 survives on HCWs hands should they not use appropriate HH. Following all protocols, all HCWs will perform a detailed surgical scrub (similar to surgeons before an operation) to make certain that all H1N1 is killed to avoid any infection of themselves or their contacts. The study will be undertaken in special, secure, negative-pressure rooms at Austin Hospital away from patient care areas to provide maximum safety conditions. All virus culture and molecular tests will be performed in the virus Identification Laboratory at the Victorian Infectious Disease Reference Laboratory (VIDRL), Melbourne. Results of the study should help identify which HH protocol provides the most protection against influenza.Read moreRead less
Safety Of Hendra Virus Anti-G Glycoprotein Monoclonal Antibody In Humans
Funder
National Health and Medical Research Council
Funding Amount
$400,000.00
Summary
Hendra virus infection in humans is a serious, and often fatal, disease. No cure exists for Hendra infection and existing treatments are ineffective. Recently, a human monoclonal antibody has shown great promise in protecting animals from developing the disease. This project aims to perform preclinical safety testing and a Phase I clinical trial to establish the safety profile of this antibody such that it can be used to prevent Hendra infection in humans exposed to the disease.
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
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