Hepatitis C virus–like particles combined with novel adjuvant systems enhance virus‐specific immune responses
Hepatitis C virus–like particles combined with novel adjuvant systems enhance virus‐specific immune responses
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DOI：
10.1053/jhep.2003.50000
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发表时间：
2003-01
期刊：
影响因子：
13.5
通讯作者：
M. Qiao;K. Murata;A. Davis;S. Jeong;T. Liang
中科院分区：
文献类型：
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作者：
M. Qiao;K. Murata;A. Davis;S. Jeong;T. Liang
我们之前已经描述了昆虫细胞中丙型肝炎病毒样颗粒（HCV-LPs）的产生，并表明用HCV-LPs免疫引起小鼠的体液和细胞免疫应答。为了进一步表征作为候选疫苗的HCV-LP，我们评估了佐剂AS 01 B（单磷酰脂质A [MPL]和QS 21）、CpG 10105以及2种佐剂的组合对AAD小鼠（HLA-A2. 1转基因小鼠）中HCV-LP免疫原性的影响。所有HCV-LP免疫小鼠（有或无佐剂）在4次肌内注射后均产生高滴度的抗HCV E1/E2抗体。然而，用HCV-LP加AS 01 B、加CpG 10105或加AS 01 B和CpG 10105的组合免疫的小鼠中的抗体滴度分别比单独HCV-LP高4、3和10倍。诱导的抗包膜抗体的同种型分析显示，单独的HCV-LP诱导了主要的免疫球蛋白（IG）G1应答。相比之下，当2种佐剂AS 01 B和CpG 10105组合时，应答变为主要的IgG 2a，而HCV-LP加AS 01 B或CpG 10105产生混合的IgG 1和IgG 2a应答，表明AS 01 B和CpG 10105促进更多的1型辅助性T细胞（Th 1）应答，并且组合2种佐剂导致相加或协同相互作用。干扰素（IFN）-γ和白细胞介素（IL）-4的CD 4+酶联免疫斑点试验结果以及产生IFN-γ的CD 8+细胞的细胞内细胞因子染色结果进一步证实了这些观察结果。总之，HCV-LP是一种有前途的抗HCV感染的候选疫苗，所用佐剂是这种方法的有效免疫增强剂。
We have previously described the generation of hepatitis C virus–like particles (HCV‐LPs) in insect cells and shown that immunization with HCV‐LPs elicited both humoral and cellular immune responses in mice. To further characterize the HCV‐LPs as a vaccine candidate, we evaluated the effects of adjuvant AS01B (monophosphoryl lipid A [MPL] and QS21), CpG 10105, and the combination of the 2 adjuvants on the immunogenicity of HCV‐LPs in AAD mice (transgenic for HLA‐A2.1). All HCV‐LP–immunized mice (with or without adjuvant) developed high titers of anti‐HCV E1/E2 antibodies after 4 injections intramuscularly. However, antibody titers in mice immunized with HCV‐LP plus AS01B, plus CpG 10105, or plus the combination of AS01B and CpG 10105 were 4, 3, and 10 times higher, respectively, than that of HCV‐LP alone. Isotype analysis of the induced anti‐envelope antibodies showed that HCV‐LP alone induced a predominant immunoglobulin (Ig) G1 response. In contrast, when the 2 adjuvants AS01B and CpG 10105 were combined, the response became predominantly IgG2a whereas HCV‐LP plus AS01B or CpG 10105 gave a mixed IgG1 and IgG2a response, indicating that AS01B and CpG 10105 promote a more T‐helper type 1 (Th1) response and that combining the 2 adjuvants results in an additive or synergistic interaction. These observations were further confirmed by the results of CD4+ enzyme‐linked immunospot assay for interferon (IFN)‐γ and interleukin (IL)‐4 and intracellular cytokine staining of IFN‐γ producing CD8+ cells. In conclusion, HCV‐LP is a promising vaccine candidate against HCV infection and the adjuvants used are potent immune enhancers for this approach.