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KMID : 0620920080400060669
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Experimental & Molecular Medicine
2008 Volume.40 No. 6 p.669 ~ p.676
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Increased in vivo immunological potency of HB-110, a novel therapeutic HBV DNA vaccine, by electroporation
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Kim Chae-Young
Kang Eun-Sung
Kim Seon-Beom
Im Se-Jin
Kim Byong-Moon
Kim Byung-Gee
Kim Han-Eol
Choi Jae-Hoon
Lee Dong-Sop
Sung Young-Chul
Yang Se-Hwan
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Abstract
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Pulse-induced permeabilization of cellular membranes, generally referred to as electroporation (EP), has been used for years as a tool to increase macromolecule uptake in tissues, including nucleic acids, for gene therapeutic applications, and this technique has been shown to result in improved immunogenicity. In this study, we assessed the utility of EP as a tool to improve the efficacy of HB-110, a novel therapeutic DNA vaccine against chronic hepatitis B, now in phase 1 of clinical study in South Korea. The potency of HB-110 in mice was shown to be improved by EP. The rapid onset of antigen expression and higher magnitude of humoral and cellular responses in electric pulse-treated mice revealed that EP may enable a substantial reduction in the dosage of DNA vaccine required to elicit a response similar in magnitude to that achievable via conventional administration. This study also showed that EP-based vaccination at 4-week-intervals elicited a cellular immune response which was about two-fold higher than the response elicited by conventional vaccination at 2-week intervals. These results may provide a rationale to reduce the clinical dose and increase the interval between the doses in the multidose vaccination schedule. Electric pulsing also elicited a more balanced immune response against four antigens expressed by HB-110: S, preS, Core, and Pol.
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KEYWORD
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electroporation, hepatitis B virus, vaccination, vaccines, DNA
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