1a.Objectives (from AD-416):
Evaluate swine influenza virus strain specific antigenic epitopes that might enable development of serological assays for pandemic H1N1 surveillance in swine. Evaluate selected antigenic epitopes and genetic factors of swine influenza virus that may lead to heterologous immunity elicited by influenza vaccines to enable development of improved vaccines with broader protective immunity against novel emerging influenza strains.
1b.Approach (from AD-416):
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. Collaborate in conducting animal studies 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.
ARS scientists at the National Animal Disease Center in Ames, Iowa, in collaboration with scientists at Iowa State University completed a series of studies successfully addressing all research objectives. Scientists evaluated swine influenza virus strain specific antigenic epitopes that might enable development of serological assays for pandemic H1N1 surveillance in swine. Four peptides from the pH1N1 virus showed potential as candidates for a pH1N1 specific immunoassay however, a specific assay for the detection of the pH1N1 viruses has proven impractical and not necessary today given the immense genetic and antigenic diversity of swine H1 influenza strains and the subsequent reassortment events that have generated new strains of H1 influenza viruses in pigs. This study did however generate novel information about linear epitopes or immunogenic regions on the influenza M1, M2 or NA proteins and has helped to generate data that will be useful to influenza researchers in dissecting antibody responses to these proteins. A series of studies on the second objective evaluated selected antigenic epitopes and genetic factors of swine influenza virus that may lead to heterologous (cross-protective) immunity elicited by influenza vaccines to enable development of improved vaccines with broader protective immunity against novel emerging influenza strains. The first study investigated the potential for the pandemic virus to cause vaccine associated enhanced respiratory disease (VAERD) in weaned pigs that were vaccinated with endemic swine influenza virus (SIV) strains and experimentally infected with pH1N1. This work established that the whole inactivated virus (WIV) vaccine induced cellular immune responses cross-reactive to the heterologous pH1N1 virus, and this was most pronounced in the CD4+CD8+ population of T cells also known as memory cells. The second study built upon the first and demonstrated natural infection and live attenuated elicit superior cellular immune responses compared with WIV, identified vaccine induced interferon gamma producing T cells as the best predictor of cross-protective immunity and also demonstrated that immune factors other than T cells are responsible for VAERD pathogenesis. Two subsequent studies found that VAERD was prevented when H1 subtype WIV vaccines contained neuraminidase (NA) protein closely matched to NA of the heterologous challenge strain, this supports a hypothesis that well-matched NA antibodies can prevent VAERD.