A novel system for constructing a recombinant highly-attenuated Vaccinia virus strain (LC16m8) expressing foreign genes and its application for the generation of LC16m8-based vaccines against herpes simplex virus 2

Natsumi Omura, Tomoki Yoshikawa, Hikaru Fujii, Miho Shibamura, Takuya Inagaki, Hirofumi Kato, Kazutaka Egawa, Shizuko Harada, Souichi Yamada, Haruko Takeyama, Masayuki Saijo

    Research output: Contribution to journalArticle

    1 Citation (Scopus)

    Abstract

    A novel system was developed for generating highly attenuated vaccinia virus LC16m8 (m8, third-generation smallpox vaccine) that expresses foreign genes. The innovations in this system are its excisable selection marker, specificity of the integration site of a gene of interest, and easy identification of clones with a fluorescent signal. Using this system, recombinant m8s, which expressed herpes simplex virus 2 (HSV-2) glycoprotein B (gB)-, gD-, or both gB and gD (gB + gD), were generated, and their efficacy was evaluated. First, the induction of a specific IgG against these HSV-2 glycoproteins in mice infected with one of these recombinant m8s was confirmed by an immunofluorescent assay. Next, mice preinfected with one of the recombinant m8s were infected with HSV-2 at a lethal dose to examine the vaccine efficacy. The fatality rate among the mice preinfected with either the recombinant gB + gD- or gD-expressing m8 significantly decreased in comparison with the control. The survival rate in male and female mice preinfected with either the recombinant gB + gD- or gD-expressing m8 increased to 100% and 60%, respectively, while most of the control mice died. In summary, this new system may be applicable to creation of a novel m8-based vaccine.

    Original languageEnglish
    Pages (from-to)229-233
    Number of pages5
    JournalJapanese Journal of Infectious Diseases
    Volume71
    Issue number3
    DOIs
    Publication statusPublished - 2018 Jan 1

    Fingerprint

    Human Herpesvirus 2
    Vaccinia virus
    Glycoproteins
    Vaccines
    Genes
    Smallpox Vaccine
    Clone Cells
    Immunoglobulin G

    Keywords

    • LC16m8
    • Vaccine
    • Vaccinia virus

    ASJC Scopus subject areas

    • Microbiology (medical)
    • Infectious Diseases

    Cite this

    A novel system for constructing a recombinant highly-attenuated Vaccinia virus strain (LC16m8) expressing foreign genes and its application for the generation of LC16m8-based vaccines against herpes simplex virus 2. / Omura, Natsumi; Yoshikawa, Tomoki; Fujii, Hikaru; Shibamura, Miho; Inagaki, Takuya; Kato, Hirofumi; Egawa, Kazutaka; Harada, Shizuko; Yamada, Souichi; Takeyama, Haruko; Saijo, Masayuki.

    In: Japanese Journal of Infectious Diseases, Vol. 71, No. 3, 01.01.2018, p. 229-233.

    Research output: Contribution to journalArticle

    Omura, Natsumi ; Yoshikawa, Tomoki ; Fujii, Hikaru ; Shibamura, Miho ; Inagaki, Takuya ; Kato, Hirofumi ; Egawa, Kazutaka ; Harada, Shizuko ; Yamada, Souichi ; Takeyama, Haruko ; Saijo, Masayuki. / A novel system for constructing a recombinant highly-attenuated Vaccinia virus strain (LC16m8) expressing foreign genes and its application for the generation of LC16m8-based vaccines against herpes simplex virus 2. In: Japanese Journal of Infectious Diseases. 2018 ; Vol. 71, No. 3. pp. 229-233.
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    abstract = "A novel system was developed for generating highly attenuated vaccinia virus LC16m8 (m8, third-generation smallpox vaccine) that expresses foreign genes. The innovations in this system are its excisable selection marker, specificity of the integration site of a gene of interest, and easy identification of clones with a fluorescent signal. Using this system, recombinant m8s, which expressed herpes simplex virus 2 (HSV-2) glycoprotein B (gB)-, gD-, or both gB and gD (gB + gD), were generated, and their efficacy was evaluated. First, the induction of a specific IgG against these HSV-2 glycoproteins in mice infected with one of these recombinant m8s was confirmed by an immunofluorescent assay. Next, mice preinfected with one of the recombinant m8s were infected with HSV-2 at a lethal dose to examine the vaccine efficacy. The fatality rate among the mice preinfected with either the recombinant gB + gD- or gD-expressing m8 significantly decreased in comparison with the control. The survival rate in male and female mice preinfected with either the recombinant gB + gD- or gD-expressing m8 increased to 100{\%} and 60{\%}, respectively, while most of the control mice died. In summary, this new system may be applicable to creation of a novel m8-based vaccine.",
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