Veterinary Vaccine (Jun 2022)
Efficacy of a plant-produced clade 2.3.4.4 H5 influenza virus-like particle vaccine in layer hens
Abstract
Outbreaks caused by Goose/Guangdong H5 highly pathogenic avian influenza (HPAI)-lineage viruses continue to occur in unprecedented numbers throughout Eurasia, the Middle East and Africa, causing billions of dollars in economic losses and the deaths or destruction of hundreds of millions of poultry, and pose a zoonotic threat. Here, a recombinant virus-like particle (VLP) displaying the hemagglutinin protein of a clade 2.3.4.4b H5N8 HPAI strain was produced in tobacco plants (Nicotiana benthamiana) and its immunogenicity with four commercial adjuvants was compared in layer hens. After two immunizations with 250 hemagglutinating unit doses, hens that received intramuscular injections of H5 VLPs formulated with Emulsigen D, Emulsigen P or Montanide ISA 71VG seroconverted with hemagglutination inhibition geometric mean titres (GMTs) of 7.3 log2 (± 1.17), 8 log2 (± 1.08) and 7.9 log2 (±1.07), respectively, but the GMT of hens inoculated by eye drop with VLPs plus Carbigen only reached 2.05 log2 (± 1.64). The H5 VLP plus Emulsigen-P vaccinated hens and a sham-vaccinated group were then challenged with a high dose of the homologous H5N8 HPAI virus. Vaccinated hens were completely protected and showed no clinical signs, whereas the sham-vaccinated birds all died within 3–4 days. The average oropharyngeal shedding in vaccinated hens was reduced by 3,487-fold and 472-fold on days 2 and 3 post challenge, respectively, whereas average cloacal shedding was reduced by 2,360,098-fold and 15,608-fold on days 2 and 3, respectively, compared to the sham-vaccinated controls. No virus was detected in the vaccinated hens after day 8 post challenge, and the plant-produced H5 VLP vaccine completely prevented H5N8 HPAI virus transmission to eggs. This highly efficacious, safe and non-toxic plant-produced H5 VLP vaccine with DIVA (differentiation of infected from vaccinated animals) capability could be rapidly produced with a yield of at least 85,000 doses per Kg of plant leaf material.
