Fowl adenovirus (FAdV) fiber-based vaccine against inclusion body hepatitis (IBH) provides type-specific protection guid

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Fowl adenovirus (FAdV) fiber‑based vaccine against inclusion body hepatitis (IBH) provides type‑specific protection guided by humoral immunity and regulation of B and T cell response Carlotta De Luca1, Anna Schachner1, Taniya Mitra2, Sarah Heidl1, Dieter Liebhart2 and Michael Hess1,2* 

Abstract  A recombinant fowl adenovirus (FAdV) fiber protein, derived from a FAdV-8a strain, was tested for its efficacy to protect chickens against inclusion body hepatitis (IBH). FAdV-E field isolates belonging to both a homotypic (FAdV-8a) and heterotypic (-8b) serotype were used as challenge. Mechanisms underlying fiber-induced protective immunity were investigated by fiber-based ELISA, virus neutralization assays and flow cytometry of peripheral blood mononuclear cells, monitoring the temporal developments of humoral and cellular responses after vaccination and challenge exposure. Birds were clinically protected from the homologous challenge and showed a significant reduction of viral load in investigated target organs, whereas fiber-based immunity failed to counteract the heterologous serotype infection. These findings were supported in vitro by the strictly type-specific neutralizing activity of fiber immune sera. In protected birds, fiber vaccination prevented a post-challenge drop of peripheral B cells in blood. Furthermore, fiber immunization stimulated ­CD4+ T lymphocyte proliferation while moderating the CD8α+ T cell response and prevented challenge-induced changes in systemic monocytes/macrophages and γδ+ T cell subpopulations. Both vaccinated and adjuvant-only injected birds experienced a priming of systemic B cells and TCRγδ+ T lymphocytes, which masked possible pre-challenge effects due to the antigen. In conclusion, within FAdV-E, recombinant fiber represents a vaccine candidate to control the adverse effects of homotypic infection by eliciting an effective humoral immunity and regulating B and T cell response, whereas the failure of heterotypic protection suggests a primordial role of humoral immunity for this vaccine. Keywords:  Fowl adenovirus, fiber, inclusion body hepatitis, vaccine, humoral immunity, cellular immunity Introduction Fowl adenoviruses (FAdVs) are non-enveloped, dsDNA viruses belonging to the family Adenoviridae, genus Aviadenovirus. The current classification recognizes five *Correspondence: [email protected] 1 Christian Doppler Laboratory for Innovative Poultry Vaccines (IPOV), University of Veterinary Medicine, Vienna, Austria Full list of author information is available at the end of the article

species based on genomic criteria (Fowl aviadenovirus A to Fowl aviadenovirus E (FAdV-A–FAdV-E)), with 12 subordinate serotypes (FAdV-1 to -8a, and -8b to -11) defined by cross-neutralization [1, 2]. Particular FAdV types, belonging to different species, are associated with three disease complexes with relevance for the commercial poultry sector on a global scale [3]. Analogous to the extent of genetic separation between the responsible strains, adenoviral gizzar