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学科主题: 临床医学
题名:
Antibodies Targeting Novel Neutralizing Epitopes of Hepatitis C Virus Glycoprotein Preclude Genotype 2 Virus Infection
作者: Deng, Kai1; Liu, Ruyu2; Rao, Huiying1; Jiang, Dong3; Wang, Jianghua1; Xie, Xingwang1; Wei, Lai1
刊名: PLOS ONE
发表日期: 2015-09-25
DOI: 10.1371/journal.pone.0138756
卷: 10, 期:9
收录类别: SCI
文章类型: Article
WOS标题词: Science & Technology
类目[WOS]: Multidisciplinary Sciences
研究领域[WOS]: Science & Technology - Other Topics
关键词[WOS]: HUMAN MONOCLONAL-ANTIBODIES ; E2 GLYCOPROTEIN ; IMMUNE-RESPONSES ; ENVELOPE ; PARTICLES ; IMMUNIZATION ; CHIMPANZEES ; PROTEIN ; SERUM
英文摘要:

Currently, there is no effective vaccine to prevent hepatitis C virus (HCV) infection, partly due to our insufficient understanding of the virus glycoprotein immunology. Most neutralizing antibodies (nAbs) were identified using glycoprotein immunogens, such as recombinant E1E2, HCV pseudoparticles or cell culture derived HCV. However, the fact that in the HCV acute infection phase, only a small proportion of patients are self-resolved accompanied with the emergence of nAbs, indicates the limited immunogenicity of glycoprotein itself to induce effective antibodies against a highly evolved virus. Secondly, in previous reports, the immunogen sequence was mostly the genotype of the 1a H77 strain. Rarely, other genotypes/subtypes have been studied, although theoretically one genotype/subtype immunogen is able to induce cross-genotype neutralizing antibodies. To overcome these drawbacks and find potential novel neutralizing epitopes, 57 overlapping peptides encompassing the full-length glycoprotein E1E2 of subtype 1b were synthesized to immunize BALB/c mice, and the neutralizing reactive of the induced antisera against HCVpp genotypes 1-6 was determined. We defined a domain comprising amino acids (aa) 192-221, 232-251, 262-281 and 292-331 of E1, and 421-543, 564-583, 594-618 and 634-673 of E2, as the neutralizing regions of HCV glycoprotein. Peptides PUHI26 (aa 444-463) and PUHI45 (aa 604-618)-induced antisera displayed the most potent broad neutralizing reactive. Two monoclonal antibodies recognizing the PUHI26 and PUHI45 epitopes efficiently precluded genotype 2 viral (HCVcc JFH and J6 strains) infection, but they did not neutralize other genotypes. Our study mapped a neutralizing epitope region of HCV glycoprotein using a novel immunization strategy, and identified two monoclonal antibodies effective in preventing genotype 2 virus infection.

语种: 英语
所属项目编号: 2012ZX10002003
项目资助者: National Science and Technology Major Project
WOS记录号: WOS:000361800700088
Citation statistics:
内容类型: 期刊论文
URI标识: http://ir.bjmu.edu.cn/handle/400002259/65403
Appears in Collections:北京大学第二临床医学院_北京大学肝病研究所_期刊论文

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作者单位: 1.Peking Univ, Peoples Hosp, Inst Hepatol, Beijing Key Lab Hepatitis C & Immunotherapy Liver, Beijing 100871, Peoples R China
2.Capital Med Univ, Liver Dis Ctr, Beijing Ditan Hosp, Beijing, Peoples R China
3.Capital Med Univ, Inst Infect Dis, Beijing Ditan Hosp, Beijing Key Lab Emerging Infect Dis, Beijing, Peoples R China

Recommended Citation:
Deng, Kai,Liu, Ruyu,Rao, Huiying,et al. Antibodies Targeting Novel Neutralizing Epitopes of Hepatitis C Virus Glycoprotein Preclude Genotype 2 Virus Infection[J]. PLOS ONE,2015,10(9).
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