Long-term efficacy of an inactivated whole particle H5N1 virus against H5N1 highly pathogenic avian influenza virus challenge in cynomolgus monkeys

Abstract

<b>Background:</b> More than 800 human cases of H5N1 highly pathogenic avian influenza virus (HPAIV) have been reported to WHO since 2003, with a mortality rate nearly 60%. Since humans are immunologically naïve to HPAIV, and HPAIV keep evolving, it may gain the ability to easily infect and spread among humans. We have reported that an inactivated whole particle H5N1 virus (WP) was effective against HPAIV challenge 5 weeks after the first vaccination. However, the long-term efficacy of WP was unknown. <b>Aim:</b> Assess the long-term efficacy of WP against H5N1 HPAIV. <b>Methods:</b> Cynomolgus monkeys, with no previous influenza A virus infection (n=6), were subcutaneously vaccinated twice with WP. Five years later, they were challenged with a human H5N1 HPAIV isolate. Autopsy was performed 7 days later, and lung RNA was extracted for RNA-Seq. Virus titers and RNA in unvaccinated control monkeys (n=3) were used for comparison. <b>Results:</b> Vaccine antigen-specific IgG peaked at 5-8 weeks after the first dose, and was maintained at a low level. Mean virus titers (log₁₀TCID₅₀/mL) on the next day after challenge were 2.6 and 0.8 in nasal swabs, 4.5 and 3.3 in tracheal swabs, and 4.4 and 3.5 in bronchial brushes, in control and vaccinated monkeys, respectively. With 577 differentially expressed genes (q&lt;0.05), Ingenuity Pathway Analysis revealed that canonical immune signaling pathways were significantly less activated in the lungs of the vaccinated monkeys. <b>Conclusion:</b> WP reduced viral replication and lung inflammation caused by H5N1 HPAIV even after 5 years from vaccination.