Efficacy of H5 subunit vaccines to protect poultry against highly pathogenic North American H5N2 avian influenza virus

Abstract

Abstract Between December 2014 and June 2015, North America experienced the H5 highly pathogenic avian influenza (HPAI) epizootic, the largest recorded animal disease outbreak to date where over 48 million commercial poultry (e.g., chickens and turkeys) were euthanized or died from viral exposure. Soon after the epizootic began, the U.S. Department of Agriculture began testing the efficacy of different vaccines as a possible future control strategy. It was unknown whether heterologous H5 vaccines would affect infection and shedding of HPAI H5 virus in experimentally infected commercial chickens and turkeys. Three vaccine technologies were evaluated for efficacy: 1) inactivated reverse genetic laboratory-generated low pathogenicity avian influenza (LPAI) H5 virus encoding H5 hemagglutinin (HA) gene (rgH5), 2) recombinant turkey herpes virus encoding H5 HA (rHVT-H5), and 3) recombinant replication-deficient alphavirus RNA particle vaccine encoding H5 HA (RP-H5). Among all experiments, the rgH5 vaccine (clade 2.3.4.4) gave the best results in preventing mortality and reducing shedding of the North American clade 2.3.4.4 HPAI H5N2 challenge virus in chickens and turkeys. The rHVT-H5 (Clade 2.2) and RP-H5 (clade 2.3.4.4) were most efficacious as a priming vaccine, followed by booster vaccinations with rgH5-inactivated or RP-H5. Heterologous prime (rHVT-H5) and boosting (RP-H5) provided 100% protection in turkeys challenged with HPAI H5N2, whereas a single dose of RP-H5 provided partial protection. Results of these studies led to the conditional approval for RP-H5 vaccine use in poultry as a control measure for future H5 HPAI outbreaks.