The application of pseudotypes to Influenza pandemic preparedness

Human and animal populations are constantly exposed to multiple influenza strains due to zoonotic spillover and rapid viral evolution driven by intrinsic error­prone replication and immunological pressure. In this context, antibody responses directed against the haemagglutinin protein on the surface of the virus are of importance since they have been shown to correlate with protective immunity. Serological techniques, detecting these responses, play a critical role in influenza pandemic preparedness in particular with regards to the measurement of vaccine immunogenicity. As the recent human pandemics (H1N1) and avian influenza outbreaks (H5 and H7) have demonstrated, there is an urgent need to be better prepared to assess the contribution of the antibody response to protection against newly emerged viruses and to evaluate the extent of pre-existing hetero-subtypic immunity in populations. This review compares pseudotype-based assays with wildtype and VLP virus assays and discusses their place in the pandemic preparedness against the influenza virus. It additionally addresses the state of the art developments of pseudotype-based assays (chimeric haemagglutinins, multiplex and post-attachment) including the development and future deployment of assay kits and approaches towards standardization to both pre-clinical and clinical endpoints. Progress towards the development of an influenza pseudotype library for the purposes of pandemic preparedness is also outlined and discussed.