Targeting influenza vaccine antigens to antigen presenting cells

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The generation of protective immune responses as early as possible in the life of the perinatal bird is a critical practical issue as pathogen challenge may occur at hatch. The targeting of vaccine antigens to dendritic cells (DC) may be used to provoke stronger and faster immune responses than are achieved with conventional vaccines. This project will seek to produce sterile immunity to avian viruses in hatchling chickens. Approaches reported in the mammalian literature include targeting specific DC cell surface molecules with either constructs of antigen-DC ligand or with specifically modified recombinant vaccine viruses. These approaches have not been reported in poultry, partly due to a lack of appropriate APC-specific reagents. The recent cloning of APC-specific molecules have now provided the tools both for targeting and the subsequent analysis of immune responses. We will initially target CD40, a costimulatory molecule cloned in John Young’s lab, and DEC 205 an endocytosis receptor cloned in this lab. This project will apply these strategies to the potentiation of vaccination against avian influenza virus (AIV). Targetting molecules will include both monoclonal antibodies and fusion proteins. These will be linked with relevant avian influenza virus antigens, and used to vaccinate chicks. Cellular and humoral immune responses will be measured and chicks challenged with low and high pathogenicity avian influenza virus.
Modification of vaccines viruses better to target DCs will be explored in collaboration with Adrian Hill’s group at Oxford. Recombinant adenovirus will be produced to include AIV genes and will utilise DC ligands to enhance the transduction of chicken DCs in vivo. It is anticipated that this project will provide data that will be used in further grant applications and approaches to industrial partners.

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