Streptococcus pneumoniae (the pneumococcus) is an important human pathogen, which is responsible for the deaths of millions of children each year in developing countries. The high morbidity and mortality associated with pneumococcal disease is also being exacerbated by the rate at which this organism is acquiring resistance to multiple antibiotics. Existing pneumococcal polysaccharide vaccines are poorly immunogenic in young children and only provide cover against a limited range of serotypes. S ....Streptococcus pneumoniae (the pneumococcus) is an important human pathogen, which is responsible for the deaths of millions of children each year in developing countries. The high morbidity and mortality associated with pneumococcal disease is also being exacerbated by the rate at which this organism is acquiring resistance to multiple antibiotics. Existing pneumococcal polysaccharide vaccines are poorly immunogenic in young children and only provide cover against a limited range of serotypes. Serotype coverage is even lower in the more immunogenic conjugate vaccines currently being developed; these will also be very expensive, thereby limiting their use in developing countries, where the need for effective paediatric vaccines is greatest. Pneumococci produce a variety of proteins which are important in causing disease, but the relative contribution of these factors at each stage of the infection process remain to be determined. Moreover, virtually nothing is known of the mechanism whereby these virulence factors are regulated in response to the external environment of the bacterium. In view of this, we are conducting a comprehensive examination of the mechanisms of pathogenesis of pneumococcal disease, with particular reference to the role of putative virulence proteins. This information is being used to develop cheap and effective vaccines based on pneumococcal protein antigens common to all serotypes.Read moreRead less
Development Of Improved Preventative Therapeutic Strategies For The Control Of Infectious Disease
Funder
National Health and Medical Research Council
Funding Amount
$4,000,000.00
Summary
A major objective of this Australia Fellowship application is to provide a mechanism whereby, for the first time in my career, I can devote myself full-time to my program of research. This program addresses an issue of global significance, namely the control of bacterial infectious diseases. These continue to cause massive global morbidity and mortality and constitute a profound threat to human health, in spite of the availability of antimicrobial drugs for over 60 years. WHO estimates that bact ....A major objective of this Australia Fellowship application is to provide a mechanism whereby, for the first time in my career, I can devote myself full-time to my program of research. This program addresses an issue of global significance, namely the control of bacterial infectious diseases. These continue to cause massive global morbidity and mortality and constitute a profound threat to human health, in spite of the availability of antimicrobial drugs for over 60 years. WHO estimates that bacterial infections are responsible for >10 million deaths p.a., and the economic impact is inestimable. For most major pathogens, vaccines are either unavailable or have serious shortcomings. Resistance to commonly used antimicrobials is increasing at an alarming rate, and modern travel has assisted the rapid global dissemination of highly resistant and virulent clones. Morbidity and mortality are also predicted to increase as a consequence of human-induced environmental changes and the growing proportion of the population with increased susceptibility to infection. Effective management of bacterial infectious diseases in the 21st century will require a two-pronged approach involving the development of cheaper and more effective vaccines, as well as novel anti-infectives refractory to known resistance mechanisms. However, formulation of optimal therapeutic and preventative strategies demands a thorough understanding of the biology of disease, particularly the complex interactions between bacterial pathogens and their human hosts. I have also played a leadership role in establishing the Pneumococcal Vaccine Consortium, which has just submitted a co-ordinated suite of multicentre proposals to PATH Vaccine Solutions to fund final preclinical testing, GMP scale-up and Phase I-II-III trials of protein-based pneumococcal vaccines that we have developed. The PATH accelerated pneumococcal vaccine development program is of enormous potential significance, because there is now a very real probability of pneumococcal protein vaccines being fast-tracked into human trials. Our aim is to create a direct pipeline from antigen discovery in the collaborators’ laboratories into the clinic. If successful, these vaccines could save millions of lives. This will be of enormous satisfaction to me personally, as it was I who originally proposed and demonstrated “proof of principle” for the vaccine potential of pneumococcal proteins, and I have been advocating assessment of their protective efficacy in humans for over 20 years. Thus, receipt of an Australia Fellowship will undoubtedly further support the internationalisation of Australian medical research.Read moreRead less
GENETIC ANALYSIS OF POLYSACCHARIDE CAPSULE BIOSYNTHESIS AND REGULATION IN STREPTOCOCCUS PNEUMONIAE
Funder
National Health and Medical Research Council
Funding Amount
$377,036.00
Summary
Streptococcus pneumoniae (the pneumococcus) is an important cause of invasive diseases such as pneumonia, meningitis and bacteraemia in humans. Many people carry this organism in the nasopharynx asymptomatically. However, in a small proportion, the organism overcomes host defences and invades the body causing life-threatening disease. An essential virulence factor of the pneumococcus is the polysaccharide capsule which protects it from the immune defences of the host during an infection. Until r ....Streptococcus pneumoniae (the pneumococcus) is an important cause of invasive diseases such as pneumonia, meningitis and bacteraemia in humans. Many people carry this organism in the nasopharynx asymptomatically. However, in a small proportion, the organism overcomes host defences and invades the body causing life-threatening disease. An essential virulence factor of the pneumococcus is the polysaccharide capsule which protects it from the immune defences of the host during an infection. Until recently, very little was known of the pneumococcal genes involved in production of this antigen. This project aims to continue characterization of these genes, and examination of the factors which regulate their expression. This regulatory mechanism may be very important, because production of increased levels of the polysaccharide capsule is believed to be an crucial step in the transition from carriage to invasion. An understanding of the molecular events involved in biosynthesis and regulation of capsule production will improve our understanding of the disease process and identify alternative targets for antimicrobial therapy.Read moreRead less