Immunization with hepatitis C virus-like particles induces humoral and cellular immune responses in nonhuman primates

被引:85
作者
Jeong, SH
Qiao, M
Nascimbeni, M
Hu, ZY
Rehermann, B
Murthy, K
Liang, TJ
机构
[1] NIDDKD, Liver Dis Sect, NIH, Bethesda, MD 20892 USA
[2] SW Fdn Biomed Res, Dept Virol & Immunol, San Antonio, TX 78227 USA
关键词
D O I
10.1128/JVI.78.13.6995-7003.2004
中图分类号
Q93 [微生物学];
学科分类号
071005 ; 100705 ;
摘要
We have previously reported the production of hepatitis C virus-like particles (HCV-LP) using a recombinant baculovirus containing the cDNA of the HCV structural proteins (core, E1, and E2). These particles resemble the putative HCN virions and are capable of inducing strong and broad Immoral and cellular immune responses in mice. Here we present evidence on the immunogenicity of HCV-LP and the effects of novel adjuvant systems in a nonhuman primate model, the baboon. Three groups of four baboons were immunized with HCV-LP, HCV-LP and adjuvant AS01B (monophosphoryl lipid A and QS21), or HCV-LP and the combination of AS01B and CpG oligodeoxynucleotides 10105. After four immunizations over an 8-month period, all animals developed HCV-specific humoral and cellular immune responses including antibodies to HCV structural proteins and gamma interferon(+) (IFN-gamma(+))CD4(+) and IFN-gamma(+)CD8(+) T-cell responses. The immunogenicity of HCV-LP was only marginally enhanced by the use of adjuvants. The overall HCV-specific immune responses were broad and long lasting. Our results suggest that HCV-LP is a potent immunogen to induce HCV-specific Immoral and cellular immune responses in primates and may be a promising approach to develop novel preventive and therapeutic modalities.
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页码:6995 / 7003
页数:9
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