Within-host model of respiratory virus shedding and antibody response to H9N2 avian influenza virus vaccination and infection in chickens

摘要

Avian influenza virus (AIV) H9N2 subtype is an infectious pathogen that can affect both the respiratory and gastrointestinal systems in chickens and continues to have an important economic impact on the poultry industry. While the host innate immune response provides control of virus replication in early infection, the adaptive immune response aids to clear infections and prevent future invasion. Modelling virus-innate immune response pathways can improve our understanding of early infection dynamics and help to guide our understanding of virus shedding dynamics that could lead to reduced transmission between hosts. While some countries use vaccines for the prevention of H9N2 AIV in poultry, the virus continues to be endemic in regions of Eurasia and Africa, indicating a need for improved vaccine efficacy or vaccination strategies. Here we explored how three type-I interferon (IFN) pathways affect respiratory virus shedding patterns in infected chickens using a within-host model. Additionally, prime and boost vaccination strategies for a candidate H9N2 AIV vaccine are assessed for the ability to elicit seroprotective antibody titres. The model demonstrates that inclusion of virus sensitivity to intracellular type-I IFN pathways results in a shedding pattern most consistent with virus titres observed in infected chickens, and the inclusion of a cellular latent period does not improve model fit. Furthermore, early administration of a booster dose two weeks after the initial vaccine is administered results in seroprotective titres for the greatest length of time for both broilers and layers. These results demonstrate that type-I IFN intracellular mechanisms are required in a model of respiratory virus shedding in H9N2 AIV infected chickens, and also highlights the need for improved vaccination strategies for laying hens.