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Vaccine. 2007 Jun 21;25(26):4960-6. Epub 2006 Dec 22.

Characterization of sequence variations in immunodominant regions of the HBV-nucleocapsid protein as a prerequisite for the development of an epitope-based vaccine.

Author information

1
Department of Internal Medicine II, Klinikum Grosshadern, University of Munich, Marchioninistrasse 15, 81377 Munich, Germany.

Abstract

BACKGROUND/AIMS:

In hepatitis B virus infection, viral elimination is dependent on an efficient antiviral T cell response which is not detectable in chronic hepatitis B. Therefore, new therapeutic concepts focus on T cell activation, such as epitope-based T cell-targeted vaccines. However, with the development of peptide-based vaccines in mind, viral mutations frequently described in hepatitis B within known immunodominant helper epitopes may have an influence on peptide selection.

METHODS:

Mutant peptides within immunodominant epitopes (aa 1-20, aa 91-105, and aa 143-157) at position 12, 14, 93, 97, 147, 151, 153, and 155 were tested with peripheral blood mononuclear and specific clone cells for their ability to induce proliferation, produce cytokines, induce T cell receptor down-regulation or antagonize wild-type activity of the hepatitis B core antigen-specific CD4+ T cell clones.

RESULTS:

Five variants could not induce T cell proliferation or cytokine production when the variants were presented alone. Coincubation with wild-type epitopes leads to T cell activation showing that the variants do not act as T cell receptor antagonists for hepatitis B virus-specific CD4+ T cells. In contrast, five other variants and wild-type peptides stimulated CD4+ T cell proliferation and production of Th1 cytokines.

CONCLUSIONS:

Our data demonstrate that frequently occurring mutations within immunodominant epitopes have rather a nonstimulatory than a strengthening effect and thus should not included in a vaccine.

PMID:
17466417
DOI:
10.1016/j.vaccine.2006.12.009
[Indexed for MEDLINE]

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