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首页> 外文期刊>Hepatology: Official Journal of the American Association for the Study of Liver Diseases >In vivo evaluation of the cross-genotype neutralizing activity of polyclonal antibodies against hepatitis C virus.
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In vivo evaluation of the cross-genotype neutralizing activity of polyclonal antibodies against hepatitis C virus.

机译：对丙型肝炎病毒的多克隆抗体的交叉基因型中和活性的体内评估。

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摘要

Control of hepatitis C virus (HCV) infection remains a huge challenge of global medical importance. Using a variety of in vitro approaches, neutralizing antibodies (nAbs) have been identified in patients with acute and chronic hepatitis C. The exact role these nAbs play in the resolution of acute HCV infection still remains elusive. We have previously shown that purified polyclonal antibodies isolated from plasma obtained in 2003 from a chronic HCV patient (Patient H) can protect human liver chimeric mice from a subsequent challenge with the autologous HCV strain isolated from Patient H in 1977 (H77). In this study we investigated whether polyclonal antibodies isolated from Patient H in 2006 (H06), which display high cross-genotype neutralizing activity in both the HCV pseudoparticle (HCVpp) and HCV cell culture (HCVcc) systems, were also able to prevent HCV infection of different genotypes (gt) in vivo. Following passive immunization with H06-antibodies, chimeric mice were challenged with the consensus strains H77C (gt1a), ED43 (gt4a), or HK6a (gt6a). In accordance with previous results, H06-antibodies prevented infection of chimeric mice with the autologous virus. However, the outcome of a homologous challenge is highly influenced by the amount of challenge virus injected. Depending on the viral genotype used, H06-antibodies were able to protect up to 50% of chimeric mice from a heterologous challenge. Animals in which the antibody pretreatment failed displayed a clear delay in the kinetics of viral infection. Sequence analysis of the recovered viruses did not suggest antibody-induced viral escape. CONCLUSION: Polyclonal anti-HCV antibodies isolated from a chronic HCV patient can protect against an in vivo challenge with different HCV genotypes. However, the in vivo protective efficacy of cross-genotype neutralizing antibodies was less than predicted by cell culture experiments.
机译：控制丙型肝炎病毒（HCV）感染仍然是全球医学重要性的巨大挑战。使用多种体外方法，已在急性和慢性丙型肝炎患者中鉴定出中和抗体（nAb）。这些nAb在解决急性HCV感染中所起的确切作用仍不清楚。先前我们已经表明，从2003年从一名慢性HCV患者（患者H）获得的血浆中分离出的纯化多克隆抗体可以保护人类肝脏嵌合体小鼠免于受到来自1977年从患者H（H77）中分离的自体HCV株的后续攻击。在这项研究中，我们调查了2006年从患者H中分离的多克隆抗体（H06）在HCV伪颗粒（HCVpp）和HCV细胞培养（HCVcc）系统中均显示出高交叉基因型中和活性，是否也能够预防HCV感染体内不同基因型的差异。用H06抗体被动免疫后，用共有株H77C（gt1a），ED43（gt4a）或HK6a（gt6a）攻击嵌合小鼠。根据先前的结果，H06抗体阻止了嵌合小鼠被自体病毒感染。但是，同源攻击的结果受注射攻击病毒的量的很大影响。根据所使用的病毒基因型，H06抗体能够保护多达50％的嵌合小鼠免受异源攻击。抗体预处理失败的动物表现出明显的病毒感染动力学延迟。回收病毒的序列分析未提示抗体诱导的病毒逃逸。结论：从慢性HCV患者中分离出的多克隆抗HCV抗体可以抵抗不同HCV基因型的体内攻击。但是，交叉基因型中和抗体的体内保护作用小于细胞培养实验所预测的。

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