國家衛生研究院 NHRI:Item 3990099045/6740
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    Please use this identifier to cite or link to this item: http://ir.nhri.org.tw/handle/3990099045/6740


    Title: Production of EV71 vaccine candidates
    Authors: Chong, P;Hsieh, SY;Liu, CC;Chou, AH;Yuan, CJ;Wu, SC;Liu, SJ;Chow, YH;Su, IJ;Klein, M
    Contributors: Division of Vaccine Research and Development
    Abstract: Enterovirus 71 (EV71) is now recognized as an emerging neurotropic virus in Asia and with Coxsackie virus (CV) it is the other major causative agent of hand-foot-mouth diseases (HFMD). Effective medications and/or prophylactic vaccines against HFMD are urgently needed. From a scientific (the feasibility of bioprocess, immunological responses and potency in animal challenge model) and business development (cost of goods) points of view, we in this review address and discuss the pros and cons of different EV71 vaccine candidates that have been produced and evaluated in animal models. Epitope-based synthetic peptide vaccine candidates containing residues 211–225 of VP1 formulated with Freund’s adjuvant (CFA/IFA) elicited low EV71 virus neutralizing antibody responses, but were protective in the suckling mouse challenge model. Among recombinant EV71 subunits (rVP1, rVP2 and rVP3) expressed in E. coli, purified and formulated with CFA/IFA, only VP1 elicited mouse antibody responses with measurable EV71-specific virus neutralization titers. Immunization of mice with either a DNA plasmid containing VP1 gene or VP1 expressed in Salmonella typhimurium also generated neutralizing antibody responses and protected animals against a live EV71 challenge. Recombinant EV71 virus-like particles (rVLP) produced from baculovirus formulated either with CFA/IFA or alum elicited good virus neutralization titers in both mice and non-human primates, and were found to be protective in the suckling mouse EV71 challenge model. Synthetic peptides or recombinant EV71 subunit vaccines (rVP1 and rVLP) formulated in alum were found to be poorly immunogenic in rabbits. Only formalin-inactivated (FI) EV71 virions formulated in alum elicited cross-neutralizing antibodies against different EV71 genotypes in mice, rabbits and non-human primates but induced weak neutralizing responses against CAV16. From a regulatory, economic and market acceptability standpoint, FI-EV71 virion vaccines are the most promising candidates and are currently being evaluated in human clinical trials. We further describe and analyze some new bioprocesses technologies that have great potential applications in EV71 vaccine development. This review also demonstrates the opportunities and challenges that the Asian vaccine industry faces today.
    Date: 2012-12
    Relation: Human Vaccine Immunotherapy. 2012 Dec;8(12):1775-1783.
    Link to: http://dx.doi.org/10.4161/hv.21739
    JIF/Ranking 2023: http://gateway.webofknowledge.com/gateway/Gateway.cgi?GWVersion=2&SrcAuth=NHRI&SrcApp=NHRI_IR&KeyISSN=2164-5515&DestApp=IC2JCR
    Cited Times(WOS): https://www.webofscience.com/wos/woscc/full-record/WOS:000313615500015
    Cited Times(Scopus): http://www.scopus.com/inward/record.url?partnerID=HzOxMe3b&scp=84872249666
    Appears in Collections:[Ih-Jen Su(2002-2015)] Periodical Articles
    [Joe Yen-Hung Chow] Periodical Articles
    [Shih-Jen Liu] Periodical Articles
    [Chia-Chyi Liu] Periodical Articles
    [Pele Choi-Sing Chong] Periodical Articles

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