Start Date: May 18, 2010
End Date: Sep 30, 2013
Conduct immunological investigations of influenza A virus components that lead to immune responses against specific epitopes that may enable serological surveillance for the 2009 A/H1N1 in swine and determine whether heterologous immunity against endemic swine influenza viruses interferes with serological surveillance methods. Conduct an animal study to determine the pathogenesis and transmissibility of selected isolates of the wild-type novel A/HINI virus from animals and correlate with genetic and antigenic changes. Conduct an animal study utilizing a reverse genetics-derived modified live vaccine in pigs and other susceptible animal hosts against pandemic A/H1N1. Additional Approach: Reverse genetics mutants will be generated to define amino acid residues in the hemagglutinin (HA) gene (or other if relevant) that are proposed to be important for aerosol transmission and/or virulence in multiple susceptible species. Naturally occurring amino acid changes were identified in the HA of pandemic H1N1 viruses from 2009. One change, S183P, has been increasing in prevalence in the human and swine populations and was present as a low frequency quasispecies in the original human isolate A/CA/04/2009. HA containing P183 appear to have an advantage in aerosol transmission based on preliminary data in swine studies at NADC and in ferret studies at University of Maryland. This study proposes making single amino acid changes at the 183 position and/or other positions demonstrated to play a role in the observed phenotype. Virus clones will be tested in vitro, in tissue explants, and in vivo in mice, ferrets, and/or swine for comparison.