Intramuscular DNA Vaccination of Juvenile Carp against Spring Viremia of Carp Virus Induces Full Protection and Establishes a Virus-Specific B and T Cell Response

Carmen W. E. Embregts, Dimitri Rigaudeau, Tomas Veselý, Dagmar Pokorová, Niels Lorenzen, Jules Petit, Armel Houel, Malte Dauber, Heike Schütze, Pierre Boudinot, Geert F. Wiegertjes, Maria Forlenza

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    Abstract

    Although spring viremia of carp virus (SVCV) can cause high mortalities in common carp, a commercial vaccine is not available for worldwide use. Here, we report a DNA vaccine based on the expression of the SVCV glycoprotein (G) which, when injected in the muscle even at a single low dose of 0.1 μg DNA/g of fish, confers up to 100% protection against a subsequent bath challenge with SVCV. Importantly, to best validate vaccine efficacy, we also optimized a reliable bath challenge model closely mimicking a natural infection, based on a prolonged exposure of carp to SVCV at 15°C. Using this optimized bath challenge, we showed a strong age-dependent susceptibility of carp to SVCV, with high susceptibility at young age (3 months) and a full resistance at 9 months. We visualized local expression of the G protein and associated early inflammatory response by immunohistochemistry and described changes in the gene expression of pro inflammatory cytokines, chemokines, and antiviral genes in the muscle of vaccinated fish. Adaptive immune responses were investigated by analyzing neutralizing titers against SVCV in the serum of vaccinated fish and the in vitro proliferation capacity of peripheral SVCV-specific T cells. We show significantly higher serum neutralizing titers and the presence of SVCV-specific T cells in the blood of vaccinated fish, which proliferated upon stimulation with SVCV. Altogether, this is the first study reporting on a protective DNA vaccine against SVCV in carp and the first to provide a detailed characterization of local innate as well as systemic adaptive immune responses elicited upon DNA vaccination that suggest a role not only of B cells but also of T cells in the protection conferred by the SVCV-G DNA vaccine.
    Original languageEnglish
    Article number1340
    JournalFrontiers in Immunology
    Volume8
    ISSN1664-3224
    DOIs
    Publication statusPublished - 2017

    Bibliographical note

    This is an open-access article distributed under the terms of the Creative Commons Attribution License (CC BY).

    Keywords

    • DNA vaccination
    • Spring viremia of carp virus
    • T cells
    • B cells
    • Rhabdovirus

    Cite this

    Embregts, Carmen W. E. ; Rigaudeau, Dimitri ; Veselý, Tomas ; Pokorová, Dagmar ; Lorenzen, Niels ; Petit, Jules ; Houel, Armel ; Dauber, Malte ; Schütze, Heike ; Boudinot, Pierre ; Wiegertjes, Geert F. ; Forlenza, Maria. / Intramuscular DNA Vaccination of Juvenile Carp against Spring Viremia of Carp Virus Induces Full Protection and Establishes a Virus-Specific B and T Cell Response. In: Frontiers in Immunology. 2017 ; Vol. 8.
    @article{6768f5302b034398a7d0e59f09ea7684,
    title = "Intramuscular DNA Vaccination of Juvenile Carp against Spring Viremia of Carp Virus Induces Full Protection and Establishes a Virus-Specific B and T Cell Response",
    abstract = "Although spring viremia of carp virus (SVCV) can cause high mortalities in common carp, a commercial vaccine is not available for worldwide use. Here, we report a DNA vaccine based on the expression of the SVCV glycoprotein (G) which, when injected in the muscle even at a single low dose of 0.1 μg DNA/g of fish, confers up to 100{\%} protection against a subsequent bath challenge with SVCV. Importantly, to best validate vaccine efficacy, we also optimized a reliable bath challenge model closely mimicking a natural infection, based on a prolonged exposure of carp to SVCV at 15°C. Using this optimized bath challenge, we showed a strong age-dependent susceptibility of carp to SVCV, with high susceptibility at young age (3 months) and a full resistance at 9 months. We visualized local expression of the G protein and associated early inflammatory response by immunohistochemistry and described changes in the gene expression of pro inflammatory cytokines, chemokines, and antiviral genes in the muscle of vaccinated fish. Adaptive immune responses were investigated by analyzing neutralizing titers against SVCV in the serum of vaccinated fish and the in vitro proliferation capacity of peripheral SVCV-specific T cells. We show significantly higher serum neutralizing titers and the presence of SVCV-specific T cells in the blood of vaccinated fish, which proliferated upon stimulation with SVCV. Altogether, this is the first study reporting on a protective DNA vaccine against SVCV in carp and the first to provide a detailed characterization of local innate as well as systemic adaptive immune responses elicited upon DNA vaccination that suggest a role not only of B cells but also of T cells in the protection conferred by the SVCV-G DNA vaccine.",
    keywords = "DNA vaccination, Spring viremia of carp virus, T cells, B cells, Rhabdovirus",
    author = "Embregts, {Carmen W. E.} and Dimitri Rigaudeau and Tomas Vesel{\'y} and Dagmar Pokorov{\'a} and Niels Lorenzen and Jules Petit and Armel Houel and Malte Dauber and Heike Sch{\"u}tze and Pierre Boudinot and Wiegertjes, {Geert F.} and Maria Forlenza",
    note = "This is an open-access article distributed under the terms of the Creative Commons Attribution License (CC BY).",
    year = "2017",
    doi = "10.3389/fimmu.2017.01340",
    language = "English",
    volume = "8",
    journal = "Frontiers in Immunology",
    issn = "1664-3224",
    publisher = "Frontiers Research Foundation",

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    Embregts, CWE, Rigaudeau, D, Veselý, T, Pokorová, D, Lorenzen, N, Petit, J, Houel, A, Dauber, M, Schütze, H, Boudinot, P, Wiegertjes, GF & Forlenza, M 2017, 'Intramuscular DNA Vaccination of Juvenile Carp against Spring Viremia of Carp Virus Induces Full Protection and Establishes a Virus-Specific B and T Cell Response', Frontiers in Immunology, vol. 8, 1340. https://doi.org/10.3389/fimmu.2017.01340

    Intramuscular DNA Vaccination of Juvenile Carp against Spring Viremia of Carp Virus Induces Full Protection and Establishes a Virus-Specific B and T Cell Response. / Embregts, Carmen W. E.; Rigaudeau, Dimitri; Veselý, Tomas; Pokorová, Dagmar; Lorenzen, Niels; Petit, Jules; Houel, Armel; Dauber, Malte; Schütze, Heike; Boudinot, Pierre; Wiegertjes, Geert F.; Forlenza, Maria.

    In: Frontiers in Immunology, Vol. 8, 1340, 2017.

    Research output: Contribution to journalJournal articleResearchpeer-review

    TY - JOUR

    T1 - Intramuscular DNA Vaccination of Juvenile Carp against Spring Viremia of Carp Virus Induces Full Protection and Establishes a Virus-Specific B and T Cell Response

    AU - Embregts, Carmen W. E.

    AU - Rigaudeau, Dimitri

    AU - Veselý, Tomas

    AU - Pokorová, Dagmar

    AU - Lorenzen, Niels

    AU - Petit, Jules

    AU - Houel, Armel

    AU - Dauber, Malte

    AU - Schütze, Heike

    AU - Boudinot, Pierre

    AU - Wiegertjes, Geert F.

    AU - Forlenza, Maria

    N1 - This is an open-access article distributed under the terms of the Creative Commons Attribution License (CC BY).

    PY - 2017

    Y1 - 2017

    N2 - Although spring viremia of carp virus (SVCV) can cause high mortalities in common carp, a commercial vaccine is not available for worldwide use. Here, we report a DNA vaccine based on the expression of the SVCV glycoprotein (G) which, when injected in the muscle even at a single low dose of 0.1 μg DNA/g of fish, confers up to 100% protection against a subsequent bath challenge with SVCV. Importantly, to best validate vaccine efficacy, we also optimized a reliable bath challenge model closely mimicking a natural infection, based on a prolonged exposure of carp to SVCV at 15°C. Using this optimized bath challenge, we showed a strong age-dependent susceptibility of carp to SVCV, with high susceptibility at young age (3 months) and a full resistance at 9 months. We visualized local expression of the G protein and associated early inflammatory response by immunohistochemistry and described changes in the gene expression of pro inflammatory cytokines, chemokines, and antiviral genes in the muscle of vaccinated fish. Adaptive immune responses were investigated by analyzing neutralizing titers against SVCV in the serum of vaccinated fish and the in vitro proliferation capacity of peripheral SVCV-specific T cells. We show significantly higher serum neutralizing titers and the presence of SVCV-specific T cells in the blood of vaccinated fish, which proliferated upon stimulation with SVCV. Altogether, this is the first study reporting on a protective DNA vaccine against SVCV in carp and the first to provide a detailed characterization of local innate as well as systemic adaptive immune responses elicited upon DNA vaccination that suggest a role not only of B cells but also of T cells in the protection conferred by the SVCV-G DNA vaccine.

    AB - Although spring viremia of carp virus (SVCV) can cause high mortalities in common carp, a commercial vaccine is not available for worldwide use. Here, we report a DNA vaccine based on the expression of the SVCV glycoprotein (G) which, when injected in the muscle even at a single low dose of 0.1 μg DNA/g of fish, confers up to 100% protection against a subsequent bath challenge with SVCV. Importantly, to best validate vaccine efficacy, we also optimized a reliable bath challenge model closely mimicking a natural infection, based on a prolonged exposure of carp to SVCV at 15°C. Using this optimized bath challenge, we showed a strong age-dependent susceptibility of carp to SVCV, with high susceptibility at young age (3 months) and a full resistance at 9 months. We visualized local expression of the G protein and associated early inflammatory response by immunohistochemistry and described changes in the gene expression of pro inflammatory cytokines, chemokines, and antiviral genes in the muscle of vaccinated fish. Adaptive immune responses were investigated by analyzing neutralizing titers against SVCV in the serum of vaccinated fish and the in vitro proliferation capacity of peripheral SVCV-specific T cells. We show significantly higher serum neutralizing titers and the presence of SVCV-specific T cells in the blood of vaccinated fish, which proliferated upon stimulation with SVCV. Altogether, this is the first study reporting on a protective DNA vaccine against SVCV in carp and the first to provide a detailed characterization of local innate as well as systemic adaptive immune responses elicited upon DNA vaccination that suggest a role not only of B cells but also of T cells in the protection conferred by the SVCV-G DNA vaccine.

    KW - DNA vaccination

    KW - Spring viremia of carp virus

    KW - T cells

    KW - B cells

    KW - Rhabdovirus

    U2 - 10.3389/fimmu.2017.01340

    DO - 10.3389/fimmu.2017.01340

    M3 - Journal article

    C2 - 29114248

    VL - 8

    JO - Frontiers in Immunology

    JF - Frontiers in Immunology

    SN - 1664-3224

    M1 - 1340

    ER -