Penton-dodecahedron of fowl adenovirus serotype 4 as a vaccine candidate for the control of related diseases

Abstract

In some serotypes of adenovirus (Ad), the penton base and attached trimeric fiber assemble into dodecameric virus-like particles called penton-dodecahedron (Pt-Dd), which can be internalized and used to deliver the vaccine antigens and drugs. Fowl adenovirus serotype 4 (FAdV-4) is an important pathogen, causing seriously economic loss to poultry industry in China and other counties. Pt-Dd particles from FAdV-4 infected cells, as well as in those infected with recombinant human Ad expressing fiber-1, fiber-2, and penton base of FAdV-4, were visualized by transmission electron microscopy. For the first time, we proved that FAdV-4 produced Pt-Dd in infected cells. Pt-Dd can also be assembled by the overexpressed recombinant proteins fiber-1, fiber-2, and penton base. Pt-Dd, as well as the recombinant proteins fiber-1, fiber-2, and penton base, were then used to immunize chickens. The humoral immune response, expression of selected immune molecules and challenge results were used to evaluate the immune efficacy of the vaccine candidates. Pt-Dd induced the highest level of enzyme-linked immunosorbent assay antibodies and significant high levels (p < 0.05) of interferonγ, interleukin-4, and major histocompatibility complex II expression in peripheral blood mononuclear cells at 48 h post-infection. The challenge results showed that Pt-Dd, inactivated FAdV-4 vaccine, and fiber-1 induced the best protection (100%), followed by fiber-2 (80%) and penton base (67%). The present study showed that FAdV-4 -Pt-Dd and recombinant fiber-1 are promising FAdV-4 vaccine candidates and could be used to replace the tissue-sourced inactivated FAdV-4 vaccine.