Increased in vivo immunological potency of HB-110, a novel therapeutic HBV DNA vaccine, by electroporation.
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.
Kim
Chae Young
CY
Research Laboratories, Dong-A Pharm. Co., Ltd. Yongin 449-900, Korea.
Kang
Eun Sung
ES
Kim
Seon Beom
SB
Kim
Han Eol
HE
Choi
Jae Hoon
JH
Lee
Dong Sop
DS
Im
Se Jin
SJ
Yang
Se Hwan
SH
Sung
Young Chul
YC
Kim
Byong Moon
BM
Kim
Byung Gee
BG
D000818:Animals; D018274:Electroporation; D006511:Hepatitis B Antigens / Q000096:biosynthesis; D017325:Hepatitis B Vaccines / Q000008:administration & dosage / Q000276:immunology*; D019694:Hepatitis B, Chronic / Q000276:immunology* / Q000517:prevention & control; D007111:Immunity, Cellular; D008297:Male; D051379:Mice; D008807:Mice, Inbred BALB C; D019444:Vaccines, DNA / Q000008:administration & dosage / Q000276:immunology*
D006511:Hepatitis B Antigens; D017325:Hepatitis B Vaccines; D019444:Vaccines, DNA