Recombinantly Expressed Chimeric Fibers Demonstrate Discrete Type-Specific Neutralizing Epitopes in the Fowl Aviadenovirus E (FAdV-E) Fiber, Promoting the Optimization of FAdV Fiber Subunit Vaccines towards Cross-Protection in vivo

Abstract

The control of inclusion body hepatitis, a disease of economic importance for chicken production worldwide, is complicated by an etiology involving multiple divergent fowl adenovirus types. The fiber protein is principally efficacious in inducing neutralizing and protective antibodies in vaccinated chickens; however, it faces limitations due to its intrinsic type specificity for neutralization.

Local cellular immune response plays a key role in protecting chickens against hepatitis-hydropericardium syndrome (HHS) by vaccination with a recombinant fowl adenovirus (FAdV) chimeric fiber protein

“…Nevertheless, immunized birds challenged with virulent FAdV-4 showed a significant reduction of clinical signs and pathological lesions ( 17 ). This marks a substantial difference compared to fiber vaccines developed from FAdV-8a and -8b fibers, whose protection against IBH correlates with the presence of serotype-specific nAbs ( 9 , 13 , 16 ). High levels of antibodies after FAdV-8a fiber vaccination have been linked to a significant increase of B cells in blood before challenge ( 13 ), whereas in the present study, the increase of circulating B cells compared to basal levels (defined by the negative control) was noted in vaccinated birds only after challenge.…”

“…However, the immune pathways associated with said protection are not fully elucidated. Whereas immunization from FAdV-8a and -8b is usually linked to a potent humoral response associated to the development of serotype-specific nAbs ( 9 , 13 , 16 , 23 – 25 ), neutralizing activity seems to be dispensable when it comes to vaccines against FAdV-4 ( 8 , 18 , 19 ). This led to speculations over the potentially crucial role of the cellular immune response against HHS infections.…”

“…A chimeric fiber protein retaining epitopes from FAdV-4 and FAdV-11, named crecFib-4/11, was designed and expressed as previously described ( 16 , 17 ). Briefly, the open reading frames of fibers from FAdV-4 (fib-2) (reference strain KR5, GenBank accession no.…”

“…In regards to subunit vaccines, the fiber protein, one of the major structural capsid components and surface antigens, has proven highly effective against HHS- and IBH-causing strains ( 8 – 15 ). Recently, the novel concept of chimeric fiber protein (crecFib) was formulated by designing a recombinant construct mimicking the full fiber structure incorporating epitopes from two distinct serotypes, in order to protect chickens from the diverse etiology of IBH ( 16 ). The concept was subsequently extended across FAdV species to obtain a singular vaccination antigen against IBH and HHS.…”

“…Even so, the immune mechanisms underlying such protection remain unclear. In fact, discrepancies between the potently neutralizing protective response against crecFib-8b/8a and an absent neutralizing activity of the crecFib-4/11 response, despite eliciting high protection, further complicate the matter ( 16 , 17 ). It has been shown previously that live and fiber-based vaccines against FAdV-4 do not always lead to the development of neutralizing antibodies (nAbs), which suggests the involvement of alternative immune pathways ( 8 , 17 , 18 ).…”