|Chrzastek, Klaudia - Orise Fellow|
Submitted to: Meeting Abstract
Publication Type: Abstract Only
Publication Acceptance Date: 1/18/2018
Publication Date: N/A
Technical Abstract: The 2014-2015 incursion of H5Nx clade 188.8.131.52 high pathogenicity avian influenza (HPAI) virus caused the largest animal health emergency in U.S. history and renewed interest in developing vaccines against these newly emergent viruses. Our previous research demonstrated several H5 vaccines with varying genetic relatedness (85-100%) to the 184.108.40.206 HPAI challenge viruses (A/Gyrfalcon/Washington/2014 H5N8 or A/Northern Pintail/Washington/2014 H5N2) provided variable protection of poultry against lethal challenge. In these studies, virus adaption to immune pressure was captured using NGS analysis of swab samples taken at various time points after challenge of vaccinated animals. Whole genome SNP analysis was performed on virus sequence obtained from two separate vaccine experiments. The variant frequency for each gene sample analyzed was determined at 1000 reads per nucleotide or above, with 5% minimum change required for inclusion. Overall, analysis of 50 samples containing complete viral genomes identified 198 amino acid (AA) mutations in either sham or vaccinated birds. The greatest percent of AA mutations were observed in the replication machinery (PA, PB1, PB2) or nucleoprotein (NP), suggesting viral adaption into poultry. Approximately 14% of mutations were observed in the hemagglutinin gene, and were mainly found in vaccinated animals. Interestingly, identical mutations in polymerase and nucleoprotein genes were observed in groups of animals that died (PB2-T683S and NP-R100K) compared to animals that survived (NP-M105I/V), implicating a potential role in pathogenesis. Taken together, these studies demonstrate that evolution of HPAI virus populations could be influenced by immune pressure and species change.