Infection of point-of-lay hens to assess the sequential events during H7N7 high-pathogenicity avian influenza emergence at a layer premises

Seekings, A. H.; Billington, E.; Mahmood, S.; Thomas, S. S.; Puranik, A.; Johnson, S.; Nunez, A.; Watson, S.; Banks, J.; Brookes, S. M.; Brown, I. H.; Slomka, M. J.

doi:10.1101/2025.07.16.665166

bioRxiv · 10.1101/2025.07.16.665166

Infection of point-of-lay hens to assess the sequential events during H7N7 high-pathogenicity avian influenza emergence at a layer premises

Seekings, A. H.·Billington, E.·Mahmood, S.·Thomas, S. S.·Puranik, A.·Johnson, S.·Nunez, A.·Watson, S.·Banks, J.·Brookes, S. M.·Brown, I. H.·Slomka, M. J.

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Abstract

H7N7 low-pathogenicity avian influenza virus (H7N7-LPAIV) incursions have preceded emergence of H7N7 high-pathogenicity (HP)AIV at several European layer hen outbreaks. Evidence from a UK layer H7N7-HPAIV (2008) outbreak informed in vivo modelling of sequential events, beginning with H7N7-LPAIV precursor incursion. Three groups of 17-week-old (point-of-lay) hens were inoculated with three precursor H7N7-LPAIV candidates which possessed: Group 1 - the classic LPAIV single-basic cleavage site (CS) (H7N7-SBCS); Group 2 - the dibasic CS (H7N7-DBCS) discovered at the outbreak (both represented direct H7N7-HPAIV (2008) precursors); Group 3 - a related European H7N7-LPAIV (2008) which possessed a DBCS within its haemagglutinin (HA) gene which was highly-conserved with the HA of the UK (2008) outbreak H7N7-HPAIV, but its other genetic segments differed. In Groups 1-3, initial H7N7-LPAIV exposure caused limited viral shedding, restricted H7-antibody responses and no deaths, by 14-days post-inoculation (dpi). H7N7-HPAIV challenge of all groups (n=8 per challenge group, including AIV-naive hens in Group 4) followed at 14 dpi. Prior H7N7-LPAIV inoculation protected against mortality due to H7N7-HPAIV challenge to varying degrees, with eight (100%), seven (87.5%), six (75%) and three (37.5%) survivors in Groups 1-4, respectively, by study-end (14-days post-challenge), when all 24 survivors had strongly seroconverted. Among challenge survivors belonging to Groups 1-3, 20/21 (95%) shed H7N7-HP, indicating that immunity acquired during initial H7N7-LPAIV exposure did not arrest H7N7-HPAIV replication. Despite prior H7N7-LPAIV incursion which elicited additional clinical protection against H7N7-HPAIV challenge, we showed how an emergent H7N7-HPAIV may represent a source for onward spread and further HPAIV outbreaks.

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Seekings, A. H., Billington, E., Mahmood, S., Thomas, S. S., Puranik, A., Johnson, S., Nunez, A., Watson, S., Banks, J., Brookes, S. M., Brown, I. H., Slomka, M. J.. 2025-07-16. Infection of point-of-lay hens to assess the sequential events during H7N7 high-pathogenicity avian influenza emergence at a layer premises. https://doi.org/10.1101/2025.07.16.665166

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