The world has suddenly been alerted to the threat of pandemic influenza with the recent deaths in Asia of patients and their close contacts from which the avian influenza H5N1 virus has been isolated. Experts believe that it is only a matter of time before this virus mutates and acquires the ability to rapidly spread within the human population. The currently available vaccines have virtually no capacity to prevent infection by a new pandemic virus. Once the virus strikes appropriate vaccines ca ....The world has suddenly been alerted to the threat of pandemic influenza with the recent deaths in Asia of patients and their close contacts from which the avian influenza H5N1 virus has been isolated. Experts believe that it is only a matter of time before this virus mutates and acquires the ability to rapidly spread within the human population. The currently available vaccines have virtually no capacity to prevent infection by a new pandemic virus. Once the virus strikes appropriate vaccines can be made against it but this procedure takes at least 6 months, the time predicted for the virus to have already spread throughout the globe. We are proposing that a vaccine designed to induce killer T cells (called CTLs) that target the conserved regions shared by all influenza viruses, could be used as a preventative measure without prior knowledge of the exact type of virus that will emerge. This sort of vaccine will not prevent against infection but will greatly lessen the severity of the disease. We have already designed a vaccine that that will induce high levels of CTLs that can greatly speed up the clearance of viruses of the type that are currently in the human population, when tested in animal models. However, we predict that a new pandemic virus will be much more vigorous in its growth and so our vaccines will have to be improved to cope with this. This project looks at ways of increasing the number and effectiveness of the CTLs that are induced by our vaccines. This will require an understanding of how we can modulate the function of other specialised cells, dendritic cells and helper T cells, that play a role in starting and maintaining the CTL response, as well as modulating the CTLs themselves.Read moreRead less
Heterosubtypic T Cell-inducing Vaccines For Influenza In Humans
Funder
National Health and Medical Research Council
Funding Amount
$352,307.00
Summary
Bird flu virus poses a large risk to the world if it mutates to become easily spread between people. If this occurs vaccines will be made to the mutated strain but there will be a time lag before these are available. We have been working on a novel vaccine that induces protective T cell immunity to parts of the virus that are common to all influenza strains and will be effective against any new virus. Our information from animal models will be used to create a human vaccine of this type .
Adapting Pandemic Influenza Interventions And Management To The Newly-emerged Virus
Funder
National Health and Medical Research Council
Funding Amount
$245,098.00
Summary
The Australian Health Management Plan for Pandemic Influenza is based on data from past and current influenza. A newly-emerged influenza strain is likely to differ in some respects. This project will develop practical ways to adapt the management plan to the emerged virus from early pandemic data. It will determine the data needed to do this efficiently, to ensure that Australia receives the greatest benefit from its antiviral drugs, vaccines and other public health interventions introduced.
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
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
Highly Pathogenic Avian Influenza (HPAI) - Improved Diagnosis With Quality Assurance Of Serological & Molecular Diagnost
Funder
National Health and Medical Research Council
Funding Amount
$249,019.00
Summary
This project aims to produce Quality Assurance (QA) algorithms to ensure accurate diagnosis of highly pathogenic avian influenza (HPAI) using serological and molecular techniques. The project will assess HPAI diagnosis accurately within the setting of other circulating respiratory illnesses, utilising a new HPAI module, ,in combination with existing modules within the Royal College of Pathologists of Australia (RCPA) Serology Quality Assurance Program (SQAP). This will ensure rapid, cost-efficie ....This project aims to produce Quality Assurance (QA) algorithms to ensure accurate diagnosis of highly pathogenic avian influenza (HPAI) using serological and molecular techniques. The project will assess HPAI diagnosis accurately within the setting of other circulating respiratory illnesses, utilising a new HPAI module, ,in combination with existing modules within the Royal College of Pathologists of Australia (RCPA) Serology Quality Assurance Program (SQAP). This will ensure rapid, cost-efficient improvements in diagnostics by utilizing existing infrastructure. The key elements of the project are: Introduction of quality assurance processes to ensure accurate diagnosis and to evaluate existing and developing laboratory testing procedures, test accuracy, and result interpretation; Involvement of human and veterinary laboratories in the QA and development processes; Production of suitable antigenic material through molecular virology as targets for HPAI antibody and molecular diagnostics in QA programs. This will thereby allow large quantities of non-infectious material for HPAI QA assessment of serological and molecular assays around Australia, using baculovirus expressed antigens and cloned gene targets respectively. These projects are designed within a short (<12 month) time frame in order to fulfil the needs of the Australian community in controlling the developing HPAI avian pandemic, and the possible human pandemic. Significant positive outcomes in the next six months are assured by the existence of current QA processes, experience in influenza research already available in the human and animal health laboratories involved, the research records of the groups, and the close existing linkages between the research, QA, diagnostic and avian virology groups.Read moreRead less
Pandemic Influenza Vaccine: Exploiting The Conserved HA Cleavage Site
Funder
National Health and Medical Research Council
Funding Amount
$243,300.00
Summary
Influenza virus needs to cleave its surface spike protein, hemagglutinin or HA, to become mature and infectious. This project is aimed at producing a vaccine that will block the cleavage thus rendering the virus non-infectious. To achieve this, we will use synthetic fragments (called peptides) of the viral HA spike protein mimicking its cleavage site to immunize mice. This will produce specific antibodies that will bind to the cleavage site while the virus is inside the infected cell, thus preve ....Influenza virus needs to cleave its surface spike protein, hemagglutinin or HA, to become mature and infectious. This project is aimed at producing a vaccine that will block the cleavage thus rendering the virus non-infectious. To achieve this, we will use synthetic fragments (called peptides) of the viral HA spike protein mimicking its cleavage site to immunize mice. This will produce specific antibodies that will bind to the cleavage site while the virus is inside the infected cell, thus preventing the viral spike protein from being cleaved and remain immature. This idea is particularly suited to fight the bird flu, as all pathogenic bird influenza viruses cleave HA spike proteins within the infected cell.Read moreRead less
Mechanisms Of B Cell Immunodominance To Influenza Virus
Funder
National Health and Medical Research Council
Funding Amount
$617,611.00
Summary
Current influenza vaccines elicit poor protection against viruses undergoing rapid change or emerging from animal reservoirs. We will define the basis for why highly conserved sites of virus vulnerability, such as the hemagglutinin "stem" domain, are poorly targeted by current vaccines and will assess novel hemagglutinin stem-based vaccines in macaque models of human influenza. Our results will guide the rational design of next-generation vaccines for influenza.
Pandemic Influenza: Developing A Model To Enhance Preperadness In The Buisness Sector
Funder
National Health and Medical Research Council
Funding Amount
$146,934.00
Summary
Businesses need to undertake pandemic influenza preparedness to protect their staff, suppliers, customers, business and the wider community. The prospect of pandemic influenza has major implications for business continuity and while the instinctive reaction may be that business is able to look after itself, small and medium sized businesses are key to Australia's economic wellbeing and thereby our physical and mental health. We also consider that without appropriate planning, and because of the ....Businesses need to undertake pandemic influenza preparedness to protect their staff, suppliers, customers, business and the wider community. The prospect of pandemic influenza has major implications for business continuity and while the instinctive reaction may be that business is able to look after itself, small and medium sized businesses are key to Australia's economic wellbeing and thereby our physical and mental health. We also consider that without appropriate planning, and because of the economic imperatives, businesses may become a key point for spreading of influenza. Small and medium sized businesses account for more than half the total private sector work-force in Australia. Experience from SARS has demonstrated that health staff spend an inordinate amount of time fielding queries from the business sector faced with an epidemic. By obtaining key information in advance, resources can be readied should a pandemic occur, and the most useful and relevant advice can be developed. The aim of this project is to establish an evidence-based approach to business preparedness for pandemic influenza. We will identify key areas of vulnerability in small and medium-sized businesses which can be targeted to enhance preparedness for pandemic influenza, and thus contribute to control of the spread of pandemic influenza in the community. Focus groups and face-to-face interviews with 200 small or medium businesses owners or managers from a range of sectors will be used to identify the critical issues for consideration pandemic preparedness planning. We will ascertain the range of current knowledge attitudes and beliefs to pandemic influenza, the extent of business continuity planning for pandemic influenza, perceived requirements to support small business to develop pandemic plans, and the most effective approaches to strategic communication and knowledge transfer. Our underlying hypothesis is based on the fact that small and medium sized businesses are inadequately informed and prepared for a pandemic, and that planning to protect staff and critical points in the business can protect both business functioning, and individual and community health. The major outcomes of this project include a self-administered intervention kit that will permit businesses to undertake their own preparedness planning.Read moreRead less