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在小鼠和猪动物模型中,表达丙型肝炎病毒包膜蛋白E2分泌形式的DNA疫苗引发强烈免疫反应。

Elicitation of strong immune responses by a DNA vaccine expressing a secreted form of hepatitis C virus envelope protein E2 in murine and porcine animal models.

作者信息

Li Yi-Ping, Kang Hye-Na, Babiuk Lorne-A, Liu Qiang

机构信息

Vaccine and Infectious Disease Organization, University of Saskatchewan, 120 Veterinary Road, Saskatoon, Saskatchewan, S7N 5E3, Canada.

出版信息

World J Gastroenterol. 2006 Nov 28;12(44):7126-35. doi: 10.3748/wjg.v12.i44.7126.

Abstract

AIM

To characterize the immunogenicity of a hepatitis C virus (HCV) E2 DNA vaccine alone or with a protein vaccine boost in murine and porcine animal models.

METHODS

A DNA vaccine expressing a secreted form of HCV E2 protein was constructed and used to vaccinate mice and piglets with or without boosting with a recombinant E2 protein vaccine formulated with CpG ODN and 10% Emulsigen. The immunogenicity of HCV E2 vaccines was analyzed by ELISA for antibody responses, MTT assay for lymphocyte proliferation, ELISPOT for the number of interferon-gamma secreting cells, and cytotoxic T lymphocyte assays.

RESULTS

Intradermal injection of E2 DNA vaccine induced strong Th1-like immune responses in mice. In piglets, E2 DNA vaccine elicited moderate and more balanced immune responses. A DNA vaccine prime and protein boost vaccination strategy induced significantly higher E2-specific antibody levels and shifted the immune response towards Th2-like ones in piglets.

CONCLUSION

A DNA vaccine expressing a secreted form of HCV E2 protein elicited E2-specific immune responses in mice and piglets. Recombinant E2 protein vaccination following DNA immunization significantly increased the antibody response in piglets. These HCV E2 vaccines may represent promising hepatitis C vaccine candidates for further investigations.

摘要

目的

在小鼠和猪动物模型中,单独或联合蛋白疫苗加强免疫来表征丙型肝炎病毒(HCV)E2 DNA疫苗的免疫原性。

方法

构建表达分泌形式HCV E2蛋白的DNA疫苗,并用于免疫小鼠和仔猪,其中部分动物在免疫后用含CpG ODN和10%乳化佐剂的重组E2蛋白疫苗进行加强免疫。通过ELISA分析HCV E2疫苗的抗体反应、MTT法检测淋巴细胞增殖、ELISPOT检测干扰素-γ分泌细胞数量以及细胞毒性T淋巴细胞检测来分析HCV E2疫苗的免疫原性。

结果

皮内注射E2 DNA疫苗在小鼠中诱导了强烈的Th1样免疫反应。在仔猪中,E2 DNA疫苗引发了适度且更为平衡的免疫反应。DNA疫苗初免和蛋白加强免疫策略在仔猪中诱导了显著更高的E2特异性抗体水平,并使免疫反应向Th2样反应转变。

结论

表达分泌形式HCV E2蛋白的DNA疫苗在小鼠和仔猪中引发了E2特异性免疫反应。DNA免疫后进行重组E2蛋白免疫显著提高了仔猪的抗体反应。这些HCV E2疫苗可能是有前景的丙型肝炎疫苗候选物,有待进一步研究。

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