A Multiple Antigen Lipophilic Adjuvant Carrier (MALAC) System
Funder
National Health and Medical Research Council
Funding Amount
$141,500.00
Summary
We have developed a Multiple-Antigen-Lipophilic-Adjuvant-Carrier (MALAC) system, based on the incorporation of lipoamino acids into a poly-functional core that provides an excellent means for enhancing the antigenicity of a potential peptide vaccine. A system is used for generating antibodies without the use of any conventional adjuvant. The system comprises two or more different antigens and one or more lipid anchor. The key of this system is a novel carrier construct, which is non-toxic and no ....We have developed a Multiple-Antigen-Lipophilic-Adjuvant-Carrier (MALAC) system, based on the incorporation of lipoamino acids into a poly-functional core that provides an excellent means for enhancing the antigenicity of a potential peptide vaccine. A system is used for generating antibodies without the use of any conventional adjuvant. The system comprises two or more different antigens and one or more lipid anchor. The key of this system is a novel carrier construct, which is non-toxic and non-immunogenic. The system contains variables, which allow optimising its structural configuration. A small library of poly-functional MALAC system will be synthesised in a controlled step-by-step way combining solution or solid phase techniques, where the exact chemical structure (and the order of the different immunological peptide sequences) of the construct is pre-determined. The antigenicity and the protection against disease will be compared with antigenicity and protection generated using conventional vaccine carriers. We also aim to exploit the particulate-forming properties of the lipo-peptide amphiphiles, to form micro-particulate oral antigens, exploiting the phenomenon of particulate uptake from the GI tract by the GALT or other intestinal sites. The MALAC constructs will be administered orally followed by the measurement of the serum IgG. Vaccination via the oral route is highly desirable, since it can overcome many of the disadvantages inherent in administration by injection - e.g. poor patient acceptability, requirement of skilled medical personnel, risk of HIV and other blood-born diseases, restricted availability and sometimes, stimulation of the wrong type of immunity. Development of vaccines for oral administration make them much more widely available, permitting self-administration and improving the operation of Public-Health vaccination programs, particularly in developing countries.Read moreRead less
A Novel Lipidic Adjuvant Carrier System For Vaccination Including Vaccination Via The Oral Route
Funder
National Health and Medical Research Council
Funding Amount
$214,593.00
Summary
We have developed a Lipid-Core-Peptide vaccine adjuvant system, based on the incorporation of lipoamino acids into poly-functional moiety that provides an excellent means for enhancing the antigenicity of a potential peptide-vaccine. As the system contains many variables, which allow substantial modifications to be made, we now wish to fully optimise its structural configuration. A library of spacer-lipoamino acid-poly-functional multiplier systems will be synthesised on solid phase. Model pepti ....We have developed a Lipid-Core-Peptide vaccine adjuvant system, based on the incorporation of lipoamino acids into poly-functional moiety that provides an excellent means for enhancing the antigenicity of a potential peptide-vaccine. As the system contains many variables, which allow substantial modifications to be made, we now wish to fully optimise its structural configuration. A library of spacer-lipoamino acid-poly-functional multiplier systems will be synthesised on solid phase. Model peptide epitopes will be synthesised on these different lipid-core systems and the antibody response will be compared with the response of the model peptide epitopes coupled to conventional vaccine carriers. The Lipid-Core Immunogen constructs including particulate systems will be administered orally as well, followed by measurement of the serum IgG response and the secretory IgA. This novel system can be used for any potential vaccine-peptide epitope and can open a new route to modern vaccination. The specific advantages of these kind of synthetic vaccines include the greater stability of the vaccine, reproducibility, eliminate the use of toxic conventional adjuvants. The key to this system is a novel carrier construct, which is non-toxic and not immunogenic. The system confers immunity with smaller risk of reaction, since it generates antibody production only against the infective microorganism. Vaccination via the oral route is highly desirable since it can overcome many of the disadvantages inherent in administration by injection - e.g. poor patient acceptability, requirement for skilled medical personnel, risk of HIV and other blood-borne diseases, restricted availability and, in cases, stimulation of the wrong type of immunity. Development of vaccines for oral administration will make them much more widely available, permitting self-administration by patients and markedly improving the operation of Public Health vaccination programs, particularly in developing countries.Read moreRead less
Optimising Prevention And Vaccination Policy For Pneumococcal Disease, Influenza And RSV In Indigenous Australians
Funder
National Health and Medical Research Council
Funding Amount
$174,933.00
Summary
Despite recommending pneumococcal vaccine in the Northern Territory since 2000 for Indigenous Australians from 15 years of age, and increasing vaccination coverage, a corresponding reduction in disease has not been observed. This study will provide an evidence base for future vaccination policy by examining whether there is an adequate immune response to pneumococcal vaccination in Indigenous Australians, and whether prior vaccination could reduce the immune response to revaccination.
The Immunogenicity Of 7-valent Pneumococcal Conjugate Vaccine In Sick Elderly People For Whom Vaccine Is Not Registered
Funder
National Health and Medical Research Council
Funding Amount
$443,800.00
Summary
The bacteria pneumococcus (also known as streptococcus pneumoniae) is the most common cause of pneumonia in the community, and a major cause of illness and death in the elderly. Rates of antibiotic resistance are also increasing. The pneumococcus is a complex bacteria, with over 80 known serotypes. Most human disease in Australia is caused by 23 of these serotypes. Australia has an ageing population. The health and wellbeing of the elderly has been identified as a national priority. Vaccination ....The bacteria pneumococcus (also known as streptococcus pneumoniae) is the most common cause of pneumonia in the community, and a major cause of illness and death in the elderly. Rates of antibiotic resistance are also increasing. The pneumococcus is a complex bacteria, with over 80 known serotypes. Most human disease in Australia is caused by 23 of these serotypes. Australia has an ageing population. The health and wellbeing of the elderly has been identified as a national priority. Vaccination and prevention of serious infections, a common cause of illness in the elderly, is an achievable public health goal. The National Health and Medical Research Council (NHMRC) of Australia recommends that adults aged 65 years and over should be immunised with 23-valent polysaccharide pneumococcal vaccine (PPV). PPV has been available long term in Australia, but the dilemma associated with its use is that it is least effective in those at greatest risk of pneumococcal disease and its complications, the sick elderly population. A new 7-valent pneumococcal conjugate vaccine (PCV-7) has been available since the end of 2000, but is currently indicated only for children, because it has never been tested in adults. This vaccine uses different technology, and is conjugated to a protein to make it more effective. Clinicals trials of PCV7 have largely been limited to children aged 0-4 years, and have shown it protects 93.9% of children under 2 years of age against invasive pneumococcal disease (IPD). Our study aims to look at the efficacy of this new vaccine, currently only registered for children, in the sub-group of the population who are at highest risk for pneumococcal disease - hospitalised elderly. We will vaccinate hospitalised elderly people with PCV or PPV and compare their immune response to the two different vaccines. If PCV is more effective than PPV, this has implications for the development and use of conjuagated pneumococcal vaccines for adults.Read moreRead less
This study will examine cellular immunity to the avian H5 influenza in people who have been previously infected with the currently circulating strains of H1 and H3 influenza, or in those who have been recently vaccinated with current influenza vaccines. This will give us an idea if there is any cross reactive immunity that may assist in developing immunity to pandemic strains of avian influenza, or may provide help in making antibody responses sooner to avian influenza vaccines once they are dev ....This study will examine cellular immunity to the avian H5 influenza in people who have been previously infected with the currently circulating strains of H1 and H3 influenza, or in those who have been recently vaccinated with current influenza vaccines. This will give us an idea if there is any cross reactive immunity that may assist in developing immunity to pandemic strains of avian influenza, or may provide help in making antibody responses sooner to avian influenza vaccines once they are developed. We will also establish assays to determine how immunogenic some new avian influenza vaccines are in mice.Read moreRead less
Cancer immunotherapy by “checkpoint blockade” boosts the immune response and leads to tumour rejection in some patients. To improve immunotherapy, information will be sought on the capacity of membrane vesicles prepared from dendritic cells (DC) to stimulate immune cells (T cells) in mice and elicit tumour rejection. Experiments are proposed to trace the fate of the vesicles after injection and improve tumour rejection by combination with checkpoint blockade and addition of cytokines.