David C. Jackson
The University of Melbourne, Australia
Title: How to elicit immediate and long-term immunity against influenza
Biography
Biography: David C. Jackson
Abstract
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- ï§, MCP-1 and TNF-ï¡ 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.