Exploiting Information Inherent in Binding Sites of Virus-Specific Antibodies: Design of An HCV Vaccine Candidate Cross-Reactive with Multiple Genotypes

Antiviral Therapy - Tập 11 Số 8 - Trang 1005-1014 - 2006
Lara Grollo1, Joseph Torresi2, Heidi E. Drummer3, Weiguang Zeng1, Nicholas A. Williamson1, David C. Jackson1,2,3
1Cooperative Research Centre for Vaccine Technology, Department of Microbiology & Immunology, The University of Melbourne, Parkville, VIC, Australia
2Department of Medicine and Center for Clinical Research Excellence, Royal Melbourne Hospital, The University of Melbourne, Parkville, VIC, Australia
3Macfarlane Burnet Institute for Medical Research and Public Health, Melbourne, VIC, Australia

Tóm tắt

Background/AimsThe role of antibody in hepatitis C virus (HCV) infection remains unclear although many reports attest to its role in viral clearance. Here we describe epitopes that are recognized by antibody present in the serum of infected patients and show that such epitopes can induce neutralizing antibodies.MethodsHuman serum containing hyperimmune anti-HCV IgG was used to extract epitopes from a library of synthetic peptides that encompassed the sequences of the E1 and E2 proteins of HCV genotype 1a H77. Peptides that were bound by IgG were identified by mass spectrometry. Assembly of these epitopes with a helper T cell determinant was then carried out in order to construct candidate epitope-based vaccines.ResultsThree distinct antigenic sites were defined in the E1E2 glycoproteins by epitopes identified by antibody present in infected individuals. Four of the peptide epitopes identified are conserved in at least three HCV genotypes and are bound by antibody present in the sera of chronically infected and convalescent individuals. Synthetic vaccines based on these epitopes elicited antibodies that are capable of (i) capturing HCV virions from the serum of viraemic patients and (ii) inhibiting HCV pseudovirus particle entry into Huh7 cells.ConclusionsThis approach exploits the information inherent in the binding sites of virus-specific antibodies and represents a novel method for the design of synthetic epitope-based vaccines.

Từ khóa


Tài liệu tham khảo

10.1016/S0264-410X(98)00415-0

10.7326/0003-4819-140-5-200403020-00010

10.1084/jem.20021756

10.1073/pnas.91.16.7792

10.1046/j.1365-2249.2002.01840.x

10.1099/0022-1317-83-7-1673

10.1073/pnas.93.26.15394

10.1073/pnas.93.5.1759

10.1006/viro.1996.0497

10.1002/hep.510250530

10.1073/pnas.0402458101

10.1016/j.vetimm.2004.12.008

10.1128/JVI.76.9.4212-4221.2002

10.1002/eji.200535217

10.1016/S0264-410X(02)00466-8

10.1128/JVI.76.19.9798-9805.2002

10.1073/pnas.0406740101

10.1073/pnas.0832180100

10.1002/hep.21088

10.1128/JVI.80.6.2654-2664.2006

10.1016/S0014-5793(03)00635-5

10.4049/jimmunol.169.9.4905

10.1046/j.0019-2805.2001.01271.x

10.1016/S0264-410X(01)00152-9

10.1128/jvi.62.1.305-312.1988

10.1128/jvi.69.11.6705-6711.1995

NCBI database. Available from: www.ncbi.nlm.nih.gov.

HCV sequence database. Available from: http://hcv.lanl.gov/content/hcv-db/classification/genotable.html.

10.4049/jimmunol.167.7.3878

10.1016/S0166-3542(01)00180-2

10.1128/jvi.68.3.1494-1500.1994

10.1074/jbc.M405098200

10.1128/JVI.73.8.6235-6244.1999

10.1128/JVI.78.17.9224-9232.2004

10.1128/JVI.73.1.11-18.1999

10.1016/S0168-8278(99)80059-2

10.1128/JVI.74.22.10407-10416.2000

10.1128/JVI.78.13.7257-7263.2004

10.1006/viro.1998.9069

10.1046/j.1365-2893.2000.00242.x

Schoofs P.G., 1988, J Immunol, 140, 611, 10.4049/jimmunol.140.2.611

10.1016/j.vaccine.2005.04.030

10.1128/JVI.78.17.9030-9040.2004

10.1128/JVI.77.3.1856-1867.2003

10.1128/JVI.00029-06

Thông tin
Thông tin xuất bản

Antiviral Therapy

Tập 11 Số 8

1005-1014

Thông tin tác giả