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bioRxiv · 10.1101/394072

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

Tang, Q.·Dang, R.·Qiu, L.·Yang, Z.·Wang, X.
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Abstract

In some serotypes of adenovirus (Ad), the penton base protein and attached trimeric fiber assemble into dodecameric virus-like particles called penton-dodecahedron (Pt-Dd), which can internalize into cells and can be used to deliver the vaccine antigen and drugs. Fowl adenovirus serotype 4 (FAdV-4) is an important poultry pathogens and causing seriously economic lost to poultry industry in China and several other counties. The produce of Pt-Dd in FAdV-4 infected cells as well as in those infected with the recombinant human Ad expressing fiber-1, fiber-2, and penton base was determine by Transmission electron microscopy (TEM). For the First time, we proved that FAdV-4 produced Pt-Dd in infected cells, which 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, cell mediate immune response (CMI), 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 high levels of CMI, showing a significantly (p < 0.05) high level of interferon {gamma}, interleukin-4, and major histocompatibility complex II expressions in peripheral blood mononuclear cells at 48 h post-infection. The challenge results showed that Pt-Dd, inactivated FAdV-4 vaccine, as well as fiber-1 induced the best protection (100%), followed by fiber-2 (80%) and penton (67%). The present study showed that FAdV-4-Pt-Dd and recombinant fiber-1 are good FAdV-4 vaccine candidates and could be used to replace the tissue-sourced inactivated FAdV-4 vaccine.\n\nImportanceFAdV-4-Pt-Dds were discovered in FAdV-4 infected cells, and which were also assembled in cells transduced with recombinant human adenovirus expressing fiber-1, fiber-2, and penton base. FAdV-4-Pt-Dds internalize into cells with high efficiency, so that it can be used for delivery vaccine antigen or drugs. Immunization chickens with Pt-Dd and fiber-1 obtained by transduction HEK-293T cells induced significant high level humoral and cellular mediated immune responses, and also 100% challenge protection in chickens indicating that they are good FAdV-4 vaccine candidates. What more, the Pt-Dd obtained by transduction HEK-293T cell would have no DNA and adenovirus contamination as adenovirus could not package in HEK-293T cells.

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Tang, Q., Dang, R., Qiu, L., Yang, Z., Wang, X.. 2018-08-17. Penton-dodecahedron of fowl adenovirus serotype 4 as a vaccine candidate for the control of related diseases. https://doi.org/10.1101/394072

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