Project 169068

Influenza A viruses evolve constantly and rapidly leading to seasonal flu epidemics and occasional but devastating flu pandemics. There is thus a need to rapidly identify new emerging influenza strains for rapid development of effective influenza vaccines. In addition, there has been a recent and important increase of influenza resistance to the only two classes of antiviral agents available (adamantanes and neuraminidase (NA) inhibitors) which limit treatment/prophylactic opportunities for infected patients and their contacts. In this research, we propose to set up a national network for a comprehensive and real-time evaluation of influenza virus evolution and for global antiviral suceptibility assessment. In brief, a panel of influenza A viruses will be collected at 4 geographically-representative Canadian virology laboratories during a major influenza outbreak or in the early phase of a pandemic. The molecular (NA and hemagglutinin (HA) gene sequencing) and antigenic properties of these viruses will be analyzed at a central laboratory. Based on sequence alignments, phylogenetic trees will be constructed to assess viral evolution over time. Similarly, phenotypic (plaque and enzymatic assays) and genotypic methods will be used to evaluate viral susceptibility or resistance to available antiviral agents. All results will be rapidly transmitted to provincial and national public health authorities. At term, this integrated network will improve public health control measures with more rationale use of antiviral agents and rapid design of effective vaccines in the case of major influenza outbreaks or pandemics.

double-blind, randomized crossover trial design