Publikation

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

Wissenschaftlicher Artikel/Review - 21.06.2007

Bereiche
PubMed
DOI

Zitation
Gruener N, Gerlach T, Ulsenheimer A, Diepolder H, Wierenga E, Zachoval R, Heeg M, Pape G, Jung M. Characterization of sequence variations in immunodominant regions of the HBV-nucleocapsid protein as a prerequisite for the development of an epitope-based vaccine. Vaccine 2007; 25:4960-6.
Art
Wissenschaftlicher Artikel/Review (Englisch)
Zeitschrift
Vaccine 2007; 25
Veröffentlichungsdatum
21.06.2007
ISSN (Druck)
0264-410X
Seiten
4960-6
Kurzbeschreibung/Zielsetzung

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.