Improving Protection Against Childhood Tuberculosis: The Influence Of BCG Vaccine Strain And Age On Protective Immunity
Funder
National Health and Medical Research Council
Funding Amount
$473,739.00
Summary
BCG vaccine is of vital importance in the fight against the increasing problem of TB worldwide, particularly in children. This project will compare the 3 most commonly used different strains of BCG vaccine to determine which produces the best protective immunity in newborns. It will also determine whether BCG at birth or at 2 months of age provides better protection. Optimising the timing and strain used for BCG immunisation would prevent large numbers of cases and deaths from TB at low cost.
Protecting Hyposplenic Children And Adults: Identifying Optimal Immunisation Regimens
Funder
National Health and Medical Research Council
Funding Amount
$472,044.00
Summary
Children and adults without normal spleen function are at massively increased risk of overwhelming infection with the pneumococcus bacteria, with 200 times the risk of death from sepsis compared with the normal community. Poor spleen function can be due to an absent spleen (eg after surgery following a car accident) or an underlying medical condition (eg thalassaemia or cancer therapy). Thousands of Australians are affected by this condition and need extra protection from daily antibiotics and a ....Children and adults without normal spleen function are at massively increased risk of overwhelming infection with the pneumococcus bacteria, with 200 times the risk of death from sepsis compared with the normal community. Poor spleen function can be due to an absent spleen (eg after surgery following a car accident) or an underlying medical condition (eg thalassaemia or cancer therapy). Thousands of Australians are affected by this condition and need extra protection from daily antibiotics and additional immunsiations against pneumococcus. A new vaccine against pneumococcus was introduced for Australian infants routinely in 2005 and has prevented many from developing pneumococcal meningitis, sepsis and pneumonia. We wish to see whether this new vaccine, when used with the older existing pneumococcal vaccine, will better protect older children and adults with poor spleen function from the devastating effects of pneumococcus. We will compare different ways of using these vaccines to try to identify the most protective vaccination plan for this vulnerable group of Australians.Read moreRead less
Immunisation is second only to clean water and sanitation as a life-saving activity. Vaccine safety is considered to be very important by the general public, the media and the health professions. With so many diseases controlled and now rare, the safety of vaccines assumes greater importance. Research is needed on new and safer vaccines, using e.g. a needle-free approach, against old foes, like influenza, and new enemies (like MERS) with vaccine safety more important than ever.
Do Respiratory Viruses Explain High Rates Of Acute Otitis Media With Perforation In Young Aboriginal Children
Funder
National Health and Medical Research Council
Funding Amount
$207,159.00
Summary
Aboriginal children living in remote communities have very high rates of acute otitis media with perforation. Antibiotics can prevent about half these episodes but long courses are needed. No studies have assessed the potential contribution of respiratory viruses to this burden. This study will use samples (already stored in freezers) from children with perforation and children without perforation to screen for respiratory viruses. Direct clinical and research implications are anticipated.
Targeting The Mannose Activation Pathway In Leishmania - Novel Drug Targets And Vaccines.
Funder
National Health and Medical Research Council
Funding Amount
$338,661.00
Summary
Leishmaniasis is a parasitic disease ranging in severity from skin lesions to fatal systemic infection. It is a serious public health problem throughout many regions of the world. Co-infection with HIV has emerged as a serious problem in Africa, South America and southern Europe. Recently, leishmaniasis has been identified in East Timor and in kangaroos in Australia. Treatment of leishmaniasis is based on chemotherapy, but currently used drugs are expensive, have high toxicity and unwanted side ....Leishmaniasis is a parasitic disease ranging in severity from skin lesions to fatal systemic infection. It is a serious public health problem throughout many regions of the world. Co-infection with HIV has emerged as a serious problem in Africa, South America and southern Europe. Recently, leishmaniasis has been identified in East Timor and in kangaroos in Australia. Treatment of leishmaniasis is based on chemotherapy, but currently used drugs are expensive, have high toxicity and unwanted side effects. They have also been compromised by the emergence of resistance in the parasite. Leishmania synthesises a range of surface molecules, which are needed for virulence and parasite survival in the host. The biosynthesis process of these molecules requires activated mannose. We have identified two novel parasite genes encoding for enzymes, which are essential for the biosynthesis of surface virulence factors. When either of these genes is deleted the parasite can no longer cause disease. This suggests that drugs targeting the two enzymes will be able to control the infection. We will produce crystals of these enzymes and solve their 3D structure using state of the art technology to screen libraries of synthetic chemicals to find candidate inhibitors of enzyme activity. When these compounds are identified we will use computer modelling to design compounds based on these inhibitors and crystal structure, which will lead to a new generation of anti-Leishmania drugs. We will also determine whether the avirulent parasites can be used as an attenuated vaccine. Recovery from infection leads to a solid immunity and protection from subsequent infection indicating that vaccination is feasible, but despite of a huge amount of research there is no antileishmanial vaccine currently available. This study will lead to potential novel antileishmanial drugs and vaccines. It will also provide fundametal new knowledge of the structure of enzymes critical for parasite virulence.Read moreRead less
Hepatitis B Virus Immunity In Indigenous And At Risk Children Who Received Hepatitis B Vaccination In Infancy
Funder
National Health and Medical Research Council
Funding Amount
$213,762.00
Summary
Hepatitis B virus (HBV) is transmitted by blood exposure or sexual contact and infection can result in chronic liver disease and liver cancer. Since 2000 Hepatitis B virus immunisation has been recommended for all infants in Australia with the first dose given at birth. However, prior to routine universal immunisation, a selective immunisation strategy was used in Australia from 1986. This targeted infants considered at high risk of HBV infection because of high prevalence in their population of ....Hepatitis B virus (HBV) is transmitted by blood exposure or sexual contact and infection can result in chronic liver disease and liver cancer. Since 2000 Hepatitis B virus immunisation has been recommended for all infants in Australia with the first dose given at birth. However, prior to routine universal immunisation, a selective immunisation strategy was used in Australia from 1986. This targeted infants considered at high risk of HBV infection because of high prevalence in their population of origin, (including Aboriginal- Torres Strait Islanders) and infants whose mother was a HBV carrier. These children, among the first to be vaccinated, are now adolescents. There have been no long-term follow-up studies in Australia, and limited studies elsewhere, to assess the extent of breakthrough infection and persistence of immunity to Hepatitis B after vaccine at birth. As onset of sexual activity is associated with an increased exposure to hepatitis B infection, booster doses may be needed, especially in high-risk individuals. This study includes 2 high risk groups - young indigenous adults in the Northern Territory and young adults born to HBV carrier mothers in central Sydney. It will measure the number of children who have been infected with HBV or are chronic carriers, compared to pre immunisation data, and also the persisting level of immunity in children who were vaccinated against HBV as an infant. Children whose blood test indicates that they have low immunity will be given a booster dose of HBV vaccine and their immune response measured. A rise in hepatitis B antibody following booster vaccination indicates that you have immunological memory and is currently considered to show protection from natural hepatitis B infection. If clinically significant HBV infections are found to be rare and immunologic memory can be demonstrated, this would provide good evidence to support the argument that booster vaccine doses are not required in the Australian context.Read moreRead less
Escape And Reversion Of Critical Immune Responses: Insights Into Effective Immunity To HIV
Funder
National Health and Medical Research Council
Funding Amount
$372,446.00
Summary
The HIV pandemic is a global emergency. The overall goal of this grant proposal is to elucidate the requirements for protective immunity to HIV. Although immune responses have some effect on HIV replication, the virus mutates and evolves to escape immune pressure. However, each mutation away from wild-type virus likely results in at least some impairment in the ability of the virus to replicate. Where efficient immune responses target regions of the virus that are critical to virus replication, ....The HIV pandemic is a global emergency. The overall goal of this grant proposal is to elucidate the requirements for protective immunity to HIV. Although immune responses have some effect on HIV replication, the virus mutates and evolves to escape immune pressure. However, each mutation away from wild-type virus likely results in at least some impairment in the ability of the virus to replicate. Where efficient immune responses target regions of the virus that are critical to virus replication, escape mutations may result in viral variants incapable of causing disease. Resulting from an exciting collaboration between HIV and theoretical biologists, we have recently identified techniques to calculate the effectiveness of immunity and the cost of subsequent immune escape variants. We will use and expand these techniques to identify immune responses that result in the most effective control of viral replication. These studies will lead to ways to improve HIV vaccines and thereby prevent HIV.Read moreRead less