Day 2 :
The University of Melbourne, Australia
Time : 10:00-10:30
David Jackson has been an active researcher in immunology and immunochemistry over the last 40 years. His research efforts are now focused on the design, assembly and evaluation of innovative vaccines which have led to pre-clinical and clinical evaluation of vaccine candidates for influenza, hepatitis C virus, Group A streptococcus, Mycobacterium tuberculosis and human papilloma virus. He has also developed candidate vaccines against methamphetamine and cocaine and against the reproductive hormone luteinizing hormone releasing hormone. He has trained more than 50 graduate, postgraduate, doctoral and postdoctoral scholars and published more than 200 original research papers, invited reviews and book chapters in immunology, chemistry, biochemistry and vaccinology. He was one of the founders of the Cooperative Research Centre for Vaccine Technology and is senior inventor of a number of patents with licenses issued to the pharmaceutical industry. One of his inventions resulted in a first-in-man clinical trial of a synthetic epitope-based vaccine against hepatitis C virus. He is co-founder of 2 start-up biotechnology companies both of which are based on his own inventions. In the last five years his work has attracted more than twenty million dollars in research grants from nationally and internationally competitive sources, industry and investors. He is a Senior Principal Research Fellow with the National Health & Medical Research Council of Australia, a Professor in The University of Melbourne and a Chief Investigator of an NH&MRC Program Grant. In 2014 he was appointed Distinguished Professor in Hokkaido University, Japan.
When delivered intranasally a single dose of the TLR-2 agonist S-[2,3-bis(palmitoyl oxy)propyl] cysteine (Pam2Cys) affords up to 99% reduction in viral loads in the lungs of mice challenged with influenza virus strains of moderate virulence and significantly reduces weight loss and mortality following challenge with highly virulent virus strains. The effect is immediate, occurring in the first day of exposure, and is achieved with a single dose of Pam2Cys. Mice treated with Pam2Cys and subsequently challenged with influenza virus also demonstrate lower rates of contact transmission when compared to naive mice. The anti-viral activity is antigen independent and associated with activation of the innate immune system through Pam2Cys-dependent recruitment of neutrophils, macrophages and soluble factors including IL-6, IL-10, IFN- , MCP-1 and TNF- into the pulmonary tract. The findings indicate that Pam2Cys is a novel anti-viral agent that can reduce both the severity of influenza infection, as well as the potential to transmit disease. An influenza vaccine formulated with Pam2Cys provides a similar immediate anti-viral effect but in addition provides anti-influenza antibodies cross reactive with the homologous, immunising strain, but also long-term heterotypic subtype immunity through the induction of cross-reactive CD8+ cytotoxic T cells. Vaccines formulated with Pam2Cys therefore would be suitable for use during influenza pandemics providing both an immediate anti-viral effect and long-term immunity. Finally, treatment with Pam2Cys also affords protection against secondary bacterial infection providing an option for the prevention of the secondary bacterial infections that often complicate the outcome of influenza.
Polish Academy of Sciences, Poland
Time : 10:30-11:00
Agnieszka Sirko is a Professor at the Institute of Biochemistry and Biophysics Polish Academy of Sciences in Warsaw, Poland. Her group is involved in work related to development of DNA vaccine against influenza virus and, in cooperation with other groups, in development of the modern, sensitive and reliable methods of influenza virus detection. She is a member of Polish Vaccine Consortium (PVC).
DNA vaccines, also called genetic vaccines, belong to a new generation of vaccines. It is known that DNA injection in the form of a plasmid or in a linear form may lead to induction of an immunological response against antigens coded by the vaccine used. The level of this response, important because of providing protection using the vaccine, depends on many factors. In addition to selection of an adequately strong antigen, ensuring its efficient expression in cells of the immunized body plays a key role. Various strategies are used in order to increase efficiency of DNA vaccines. They are related to modifications of expression cassette, use of various adjuvants, both biological and chemical adjuvants, use of various carriers, various administration routes or immunization in combination with other vaccines. The overview of the approaches used in our laboratory to improve the efficacy of the DNA vaccine against H5N1 virus will be presented. The basal construct used in our work encodes the full length H5 HA, however we have introduced modifications inside and outside of the HA coding region. The efficacy of several variants of such DNA vaccine was tested in two model animals, mice and chickens along with several different adjuvants. In many cases we have observedenhanced expression of the HA antigen and an improved immunological response to the vaccine.