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.
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
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