The efficacy of an inactivated avian influenza H5N1 vaccine against an African strain of HPAI H5N8 (clade 2.3.4.4 B).

Highly pathogenic avian influenza (HPAI) viruses from the Goose/Guangdong/96-lineage emerged in Southeast Asia and subsequently spread to the Middle East, Africa and Europe, infecting a range of birds and mammals (including humans). This lineage of H5 viruses can efficiently establish itself in wild birds after circulating among gallinaceous poultry, facilitating reassortment with low pathogenic avian influenza (LPAI) virus strains, enhancing dispersal over long distances and contributing to endemicity. The detection of HPAI H5N8 virus (clade 2.3.4.4B) in 2017 in the Mpumalanga Province of South Africa marked the beginning of an epidemic that devastated the South African poultry industry. Vaccines were tested to assess protection against the circulating field strain. This article describes the performance of a reverse genetics inactivated H5N1 vaccine from Zoetis (RG-H5N1), with 96.1% identity to the circulating HPAI H5N8 virus. Two locally formulated benchmarks, one containing an H5N8 antigen homologous to the field strain (Benchmark-H5N8), the other containing a heterologous (87.6% identity to field virus) LPAI H5N1 antigen (Benchmark-H5N1), were included for comparison. Efficacy was assessed in specific pathogen-free (SPF) chickens using a prime-boost approach (injections at days 21 and 45), followed by a challenge with a South African HPAI H5N8 isolate (70 days of age). The Zoetis RG-H5N1 vaccine and Benchmark-H5N8 outperformed the Benchmark-H5N1 in terms of humoral response against the H5N8 antigen and reduction of shedding. The Zoetis RG-H5N1 vaccine protected 100% of the chickens against clinical disease and death. This study confirmed that antigenically matched inactivated vaccines could induce robust protection and markedly reduce viral shedding.Conditionally licensed vaccine protected against HPAI H5N8 (clade 2.3.4.4B).Complete protection against clinical disease and mortality.Drastic reduction of viral shedding after challenge.