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* Clinic for Rheumatology and Clinical Immunology, University of Bern, Bern, Switzerland;
Massachusetts General Hospital and Harvard Medical School, Partners AIDS Research Center, Boston, MA 02129;
Microsoft Research, Redmond, WA 98052;
Department of Medicine, Ospedale Regionale di Lugano, Lugano, Switzerland;
¶ Institucio Catalana de Recerca i Estudis Avancats (ICREA), Barcelona, Spain; and
|| Irsicaixa Foundation, Badalona, Spain
Hepatitis C virus (HCV) vaccine efficacy may crucially depend on immunogen length and coverage of viral sequence diversity. However, covering a considerable proportion of the circulating viral sequence variants would likely require long immunogens, which for the conserved portions of the viral genome, would contain unnecessarily redundant sequence information. In this study, we present the design and in vitro performance analysis of a novel "epitome" approach that compresses frequent immune targets of the cellular immune response against HCV into a shorter immunogen sequence. Compression of immunological information is achieved by partial overlapping shared sequence motifs between individual epitopes. At the same time, sequence diversity coverage is provided by taking advantage of emerging cross-reactivity patterns among epitope variants so that epitope variants associated with the broadest variant cross-recognition are preferentially included. The processing and presentation analysis of specific epitopes included in such a compressed, in vitro-expressed HCV epitome indicated effective processing of a majority of tested epitopes, although re-presentation of some epitopes may require refined sequence design. Together, the present study establishes the epitome approach as a potential powerful tool for vaccine immunogen design, especially suitable for the induction of cellular immune responses against highly variable pathogens.
The costs of publication of this article were defrayed in part by the payment of page charges. This article must therefore be hereby marked advertisement in accordance with 18 U.S.C. Section 1734 solely to indicate this fact.
1 This work was supported by grants from the Swiss National Science Foundation (Grant 3200B0-103874) and the European Community (European Community Network VIRGIL).
2 Address correspondence and reprint requests to Dr. Christian Brander, at the current address: Laboratori de Retrovirologia, Fundació irsiCaixa, Hospital Universitari Germans Trias i Pujol, Ctra del Canyet s/n, 08916 Badalona, Barcelona, Catalonia, Spain. E-mail address: cbrander{at}irsicaixa.es
3 Abbreviations used in this paper: HCV, hepatitis C virus; B-LCL, EBV-transformed B cell line; NS3, nonstructural protein; OLP, overlapping peptide.
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