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

Kelly P. Burke, Supriya Munshaw, William Osburn, Jordana Levine, Lin Liu, John Sidney, Alessandro Sette, Stuart Campbell Ray, Andrea Cox

Research output: Contribution to journalArticle

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 (HCV) vaccine sequences generated using three rational approaches: combining epitopes with predicted tight binding to the MHC, consensus sequence (most common amino acid at each position), and 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 IFN-γ T cell response in HLA-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 did T cells expanded with either consensus sequence or naturally occurring sequence variants. These data support the use of representative sequence in HCV vaccine design.

Original languageEnglish (US)
Pages (from-to)5177-5188
Number of pages12
JournalJournal of Immunology
Volume188
Issue number10
DOIs
StatePublished - May 15 2012

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Virus Diseases
Hepacivirus
T-Lymphocytes
Vaccines
Consensus Sequence
Hepatitis C
Epitopes
Amino Acids
Peptides
Population

ASJC Scopus subject areas

  • Immunology

Cite this

Immunogenicity and cross-reactivity of a representative ancestral sequence in hepatitis C virus infection. / Burke, Kelly P.; Munshaw, Supriya; Osburn, William; Levine, Jordana; Liu, Lin; Sidney, John; Sette, Alessandro; Ray, Stuart Campbell; Cox, Andrea.

In: Journal of Immunology, Vol. 188, No. 10, 15.05.2012, p. 5177-5188.

Research output: Contribution to journalArticle

Burke, Kelly P. ; Munshaw, Supriya ; Osburn, William ; Levine, Jordana ; Liu, Lin ; Sidney, John ; Sette, Alessandro ; Ray, Stuart Campbell ; Cox, Andrea. / Immunogenicity and cross-reactivity of a representative ancestral sequence in hepatitis C virus infection. In: Journal of Immunology. 2012 ; Vol. 188, No. 10. pp. 5177-5188.
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