NDLI: Immunogenicity and cross-reactivity of a representative ancestral sequence in HCV infection 1

Content Provider	PubMed Central
Author	Burke, Kelly P. Munshaw, Supriya Osburn, William O. Levine, Jordana Liu, Lin Sidney, John Sette, Alessandro Ray, Stuart C. Cox, Andrea L.
Abstract	Vaccines designed to prevent or to treat hepatitis C viral infection must achieve maximum cross reactivity against widely divergent circulating strains. Rational approaches for sequence selection to maximize immunogenicity and minimize genetic distance across circulating strains may enhance vaccine induction of optimal cytotoxic T cell responses. We assessed T cell recognition of potential hepatitis C virus vaccine sequences generated using three rational approaches: 1) combining epitopes with predicted tight binding to the major histocompatibility complex (MHC), 2) consensus sequence (most common amino acid at each position), and 3) representative ancestral sequence that had been derived using Bayesian phylogenetic tools. No correlation was seen between peptide MHC binding affinity and frequency of recognition as measured by an interferon-gamma T cell response in human leukocyte antigen-matched HCV infected individuals. Peptides encoding representative, consensus, and natural variant sequences were then tested for the capacity to expand CD8 T cell populations and to elicit cross-reactive CD8 T cell responses. CD8+ T cells expanded with representative sequence HCV generally more broadly and robustly recognized highly diverse circulating HCV strains than T cell expanded with either consensus sequence or naturally occurring sequence variants. These data support the use of representative sequence in HCV vaccine design.
Related Links	http://dx.doi.org/10.4049/jimmunol.1103008
Ending Page	5188
Page Count	12
Starting Page	5177
File Format	PDF
ISSN	00221767
e-ISSN	15506606
Journal	Journal of Immunology (Baltimore, Md. : 1950)
Issue Number	10
Volume Number	188
Language	English
Publisher Date	2012-05-15
Access Restriction	Open
Subject Keyword	Medicine(all) Research in Higher Education
Content Type	Text
Resource Type	Article
Subject	Immunology and Allergy Immunology

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Immunogenicity and cross-reactivity of a representative ancestral sequence in hepatitis C virus infection.

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