In vitro assay for neutralizing antibody to hepatitis C virus:: Evidence for broadly conserved neutralization epitopes

被引:253
作者
Bartosch, B
Bukh, J
Meunier, JC
Granier, C
Engle, RE
Blackwelder, WC
Emerson, SU
Cosset, FL
Purcell, RH
机构
[1] NIAID, Infect Dis Lab, NIH, Bethesda, MD 20892 USA
[2] Ecole Normale Super Lyon, INSERM U412, Lab Vectorol Retrovirale & Therapie Gen, F-69364 Lyon 07, France
关键词
D O I
10.1073/pnas.2335981100
中图分类号
O [数理科学和化学]; P [天文学、地球科学]; Q [生物科学]; N [自然科学总论];
学科分类号
07 ; 0710 ; 09 ;
摘要
Our understanding of the humoral immune response to hepatitis C virus (HCV) is limited because the virus can be studied only in humans and chimpanzees and because previously described neutralization assays have not been robust or simple to perform. Nevertheless, epidemiologic and laboratory studies suggested that neutralizing Ab to HCV might be important in preventing infection. We have recently described a neutralization assay based on the neutralization of pseudotyped murine retrovirus constructs bearing HCV envelope glycoproteins on their surface. We have applied the assay to well characterized clinical samples from HCV-infected patients and chimpanzees, confirmed the existence of neutralizing Ab to HCV, and validated most previously reported neutralizations of the virus. We did not find neutralizing anti-HCV in resolving infections but did find relatively high titers (>1:320) of such Ab in chronic infections. Neutralizing Ab was directed not only to epitope(s) in the hypervariable region of the E2 envelope protein but also to one or more epitopes elsewhere in the envelope of the virus. Neutralizing Ab was broadly reactive and could neutralize pseudotype particles bearing the envelope glycoproteins of two different subgenotypes (1a and 1b). The ability to assay neutralizing anti-HCV should permit an assessment of the prospects for successful Ab-mediated passive and active immunoprophylaxis against hepatitis C.
引用
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页码:14199 / 14204
页数:6
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