Abstracts (complete list) - Wissenschaft Online

Petra Riedl, Kurt Reifenberg, Joerg Reimann, Reinhold Schirmbeck
Mono-specific, hepatic CD8 T cell responses primed by
cationic peptide/oligonucleotide complexes suppress viral
replication in HBV transgenic mice
Preclinical mouse models are informative to explore the possibilities for specific immune
interventions in chronic viral infection. We describe a novel Hepatitis B Virus (HBV)specific
transgenic (tg) mouse model (1.4HBV-Smut mice). Due to a point mutation in
the translational start codon of the small HBV surface protein (HBs), no infectious viral
particles can be assembled.
We tested if hepatic CD8 T cell responses can be elicited by a peptide-based vaccination
strategy in which an antigenic, Kb-restricted HBs peptide (S190-197; VWLSVIWM) is
fused to a cationic HIV-tat derived peptide (RKKRRQRRR). Positively charged fusion
peptides are quantitatively complexed with negatively charged immunostimulating
oligonucleotides (ODN). In non-transgenic mice, HBs-encoding plasmid DNA- and
peptide- based vaccination protocols efficiently primed Kb/S190-197-specific CD8 T cell
responses. In contrast, only the peptide/oligonucleotide vaccine (but not the pCI/S DNA
vaccine) elicited Kb/S190-197 specific CD8 T cell responses in 1.4HBV-Smut mice. CD8
T cells accumulate in the livers of tg mice and efficiently inhibit HBV replication. Thus,
minimal cationic peptide/ODN vaccines are attractive tools that elucidate cellular and
molecular events that lead to a monospecific, therapeutic CD8 T cell response in the
HBV expressing liver.