Attenuation of coxsackievirus B3 by VP2 mutation and its application as a vaccine against virus-induced myocarditis and pancreatitis

Jung Hyun Park, Dae Sun Kim, Young Joo Cho, Yeon Jung Kim, Soo Young Jeong, Seung Min Lee, Seong Joo Cho, Cheol Won Yun, Inho Jo, Jae Hwan Nam

    Research output: Contribution to journalArticlepeer-review

    28 Citations (Scopus)

    Abstract

    Coxsackievirus B3 (CVB3) is a common agent of viral myocarditis, a major cause of sudden cardiac death, and ultimately dilated cardiomyopathy. However, there is no vaccine in clinical use. In this study, we identified the conserved amino acid sequences in the C-terminal region of the VP2 of the coxsackievirus B group and some echoviruses. The mutant virus, YYFF, with phenylalanines substituted for two tyrosines in these conserved sequences was highly attenuated in vivo and could induce a high neutralizing antibody titer and a cytotoxic T-lymphocyte response against CVB3. Thereby, mutant-virus-immunized mice showed a 100% survival rate and protection against inflammation of the heart and pancreas after lethal dose challenge. Thus, this mutant virus is a good candidate for an attenuated CVB3 vaccine.

    Original languageEnglish
    Pages (from-to)1974-1983
    Number of pages10
    JournalVaccine
    Volume27
    Issue number13
    DOIs
    Publication statusPublished - 2009 Mar 18

    Bibliographical note

    Funding Information:
    We are grateful to Eun-Kyung Kim for the statistical analysis and to Dr. Randal Johnston for critical reading and editing. This work was supported by grants from the Korea Health 21 R&D project, the Ministry of Health & Welfare, Republic of Korea (A050768), the KNIH, the KFDA, the Gyeonggi Regional Research Center (GRRC) of the Catholic University of Korea, and the Research Fund, 2008 of the Catholic University of Korea as well as the Ministry of Knowledge Economy (MKE) and Korea Industrial Technology Foundation (KOTEF) through the Human Resource Training Project for Strategic Technology

    Keywords

    • Attenuated vaccine
    • Coxsackievirus
    • VP2

    ASJC Scopus subject areas

    • Molecular Medicine
    • General Immunology and Microbiology
    • General Veterinary
    • Public Health, Environmental and Occupational Health
    • Infectious Diseases

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