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Improvement of a recombinant avian avulavirus serotype 10 vectored vaccine by the addition of untranslated regions

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  • Improvement of a recombinant avian avulavirus serotype 10 vectored vaccine by the addition of untranslated regions


    Vaccine. 2019 Nov 9. pii: S0264-410X(19)31500-2. doi: 10.1016/j.vaccine.2019.10.098. [Epub ahead of print] Improvement of a recombinant avian avulavirus serotype 10 vectored vaccine by the addition of untranslated regions.

    Tsunekuni R1, Tanikawa T2, Nakaya T3, Saito T4.
    Author information

    1 Division of Transboundary Animal Disease, National Institute of Animal Health, National Agriculture and Food Research Organization, 3-1-5 Kannondai, Tsukuba, Ibaraki 305-0854, Japan. Electronic address: tune@affrc.go.jp. 2 Division of Transboundary Animal Disease, National Institute of Animal Health, National Agriculture and Food Research Organization, 3-1-5 Kannondai, Tsukuba, Ibaraki 305-0854, Japan. Electronic address: ttanikawa@affrc.go.jp. 3 Department of Infectious Diseases, Graduate School of Medical Science, Kyoto Prefectural University of Medicine, Kajii-cho, Kawaramachi-Hirokoji, Kamigyo-ku, Kyoto 602-8566, Japan. Electronic address: tnakaya@koto.kpu-m.ac.jp. 4 Division of Transboundary Animal Disease, National Institute of Animal Health, National Agriculture and Food Research Organization, 3-1-5 Kannondai, Tsukuba, Ibaraki 305-0854, Japan; United Graduate School of Veterinary Sciences, Gifu University, 1-1 Yanagido, Gifu City, Gifu 501-1193, Japan. Electronic address: taksaito@affrc.go.jp.

    Abstract

    BACKGROUND:

    We have previously developed a recombinant avian avulavirus serotype 10 (rAAvV-10/HA) expressing the hemagglutinin (HA) gene of a highly pathogenic avian influenza virus (HPAIV) as an emergency vaccine for poultry. rAAvV-10/HA can overcome the activity of the anti-AAvV-1 (Newcastle disease virus) antibody acquired by commercial chickens upon routine vaccination. Most chickens do not have the anti-AAvV-10 antibody, which could interfere with the vaccine efficacy. However, the vaccine efficacy of rAAvV-10/HA is not satisfactory in chickens even though it affords protection against an HPAIV challenge. In the present study, we improved the rAAvV-10/HA vaccine by enhancing the expression of the exogenous HA protein.
    METHODS:

    The 5' and 3' untranslated regions (UTR) of each AAvV-10 gene were flanked with the exogenous HA gene cassette to modify rAAvV-10/HA, yielding different rAAv10-UTRs. As a control, rAAv10-nonUTR that did not contain any UTRs was generated. The effects of UTRs on mRNA transcription, HA protein expression, and vaccine efficacy were then examined using embryonated chicken eggs and white leghorn chickens.
    RESULTS:

    The proportion of the HA gene mRNA among the vector-derived mRNAs (1.55-1.84-fold increase vs. the control) and HA protein levels (148-1151-fold increase vs. the control) in cells infected with rAAv10-UTRs were higher than in those infected with rAAv10-nonUTR. In vivo, vaccination of chickens with rAAv10-UTRs resulted in 100% protection against an HPAIV challenge. No chickens vaccinated with rAAv10-NP-UTR, rAAv10-F-UTR, or rAAv10-HN-UTR shed the virus in the throat and cloaca swabs. By contrast, rAAv10-nonUTR vaccination offered 70% protection, with 50% of chickens shedding the virus in the cloaca or throat swabs after the challenge. We conclude that the AAvV-10 UTRs can enhance the expression of the exogenous HA gene, resulting in improved efficacy of the rAAvV-10/HA vector vaccine. This improvement aids in the protection of flocks worldwide from the highly pathogenic avian influenza.
    Copyright ? 2019 The Author(s). Published by Elsevier Ltd.. All rights reserved.


    KEYWORDS:

    Avian avulavirus (AAvV); Emergency vaccination; Highly pathogenic avian influenza (HPAI); Untranslated region (UTR); Vaccine vector

    PMID: 31718900 DOI: 10.1016/j.vaccine.2019.10.098

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