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
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
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
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
The Use Of Inulin-based Adjuvants To Enhance The Effectiveness And Population Coverage Of Influenza Vaccination
Funder
National Health and Medical Research Council
Funding Amount
$250,393.00
Summary
A major obstacle in the development of effective vaccines to protect against bird flu (avian influenza) is the difficulty in producing enough vaccine in a short enough time to be able to protect the population should bird flu become a problem in the human population. Our research is focused on a technique to make vaccines much more effective and thereby reduce the amount of vaccine needed for each person. This would allow many more people to be protected with the same amount of vaccine. This tec ....A major obstacle in the development of effective vaccines to protect against bird flu (avian influenza) is the difficulty in producing enough vaccine in a short enough time to be able to protect the population should bird flu become a problem in the human population. Our research is focused on a technique to make vaccines much more effective and thereby reduce the amount of vaccine needed for each person. This would allow many more people to be protected with the same amount of vaccine. This technology is known as a vaccine adjuvant and we have developed a unique adjuvant based on a natural plant sugar called inulin that has the potential to dramatically enhance existing and new flu vaccines.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
Novel, High-throutyput Platform For Rapid Identification, Quantintation, Differential Diagnosis, And Resistance Testing
Funder
National Health and Medical Research Council
Funding Amount
$333,362.00
Summary
This proposal utilizes a newly invented process (multiplex tandem polymerase chain reaction, MT-PCR) to measure multiple (up to 100) genetic targets (eg RNA or DNA) in one sample. A range of different virus and bacterial genes can be detected, including those which make the influenza virus different (eg H1N1 or H5N1) and allow it to bypass vaccine immunity or resist drug therapy (due to neuraminidase inhibitor resistance). We will simultaneously target infections which are influenza-like (ILI) o ....This proposal utilizes a newly invented process (multiplex tandem polymerase chain reaction, MT-PCR) to measure multiple (up to 100) genetic targets (eg RNA or DNA) in one sample. A range of different virus and bacterial genes can be detected, including those which make the influenza virus different (eg H1N1 or H5N1) and allow it to bypass vaccine immunity or resist drug therapy (due to neuraminidase inhibitor resistance). We will simultaneously target infections which are influenza-like (ILI) or which might make influenza infection worse (eg staphylococcal pneumonia) as well as their resistance genes (eg MRSA). The test is rapid and automated and includes a specimen processing (DNA and RNA extraction) function that is being developed in parallel. We expect to be able to conduct high-throughput screening of multiple samples for a limited number of targets or conduct multiple tests on fewer specimens, simply by adjusting assay configuration. Measurement of the rise and fall in concentrations of influenza virus in infected persons will allow us to understand when they are no longer infectious to others, to predict when they are getting better or worse, and allow us to better understand the pattern of illness in people who are immunized against influenza or on drug therapy, or are in some other special category (eg immune compromise due to organ transplantation). While this will be able to be rolled out by our industry partners in the event of an influenza pandemic, it does not require an outbreak for successful development, and has value well beyond influenza diagnosis.Read moreRead less
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
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
Simplified Process Methods For Mass Vaccine Manufacture
Funder
National Health and Medical Research Council
Funding Amount
$158,393.00
Summary
The ideal way to protect against pandemic bird flu is to vaccinate all Australians as soon as possible after a dangerous strain starts to spread. Current manufacturing technology, which begins by making an infectious virus in chicken eggs, is unable to quickly deliver a mass vaccine to the entire Australian population. The existing process is slow, meaning that it will take several months before enough vaccine is available even to protect personnel working in essential services. The product from ....The ideal way to protect against pandemic bird flu is to vaccinate all Australians as soon as possible after a dangerous strain starts to spread. Current manufacturing technology, which begins by making an infectious virus in chicken eggs, is unable to quickly deliver a mass vaccine to the entire Australian population. The existing process is slow, meaning that it will take several months before enough vaccine is available even to protect personnel working in essential services. The product from chicken eggs is rendered safe after manufacture by breaking the virus structure. This make then break strategy reduces vaccine effectiveness meaning that even fewer individuals can be effectively protected per vaccine batch. Recent scientific progress has demonstrated that it is possible to make a non-infectious empty virus shell (a so-called virus-like particle) inside cells. This new product is able to provide full protection against a lethal influenza challenge, when administered nasally. However, these particles are very difficult to purify from contaminants that are packaged into the particles during manufacture in cells. These contaminants can cause an adverse reaction when the product is given to humans, meaning that although the product is effective it remains difficult to mass produce. A manufacturing problem remains. To overcome this manufacturing problem we will seek to assemble vaccine particles in vitro, building the particle from purified protein. Existing technology for manufacturing pure pharmaceutical protein is well-established and safe, and allows mass manufacture of contaminant-free product. This new make don't break manufacturing strategy is similar to that chosen by Merck to deliver a safe and effective vaccine, for cervical cancer, to mass market. Our key aim is to adapt this efficient manufacturing strategy to the manufacture of influenza vaccine. If successful, we will be able to immunize the Australian population using existing national biomanufacturing capability, within weeks of new strain identification, and without the requirement for high-level containment during manufacture.Read moreRead less