Background/Aims
Quasispecies are likely responsible for virus escape from host immune surveillance.
The aim of this study was to enhance the immune response against varied sequences
within the HDV quasispecies in an attempt to control chronic delta hepatitis.
Methods
The HLA-A2 restricted peptides spanning aa 43–51 of HDAg and three variant peptides
bearing single amino acid substitutions were synthesized. Their immunogenicity and
capacity to induce effective CTL responses were studied in HHD-2 mice.
Results
Native HDV epitope produced limited cytotoxic immune response. Two modified HDV peptides
(HDV 43–51 1Y; tyrosine substitution in positive 1, and 43–51 3A; alanine substitution
in position 3) could enhance not only the binding affinity with HLA-A2.1 molecules
but also the immunogenicity. Ex vivo interferon-γ ELISPOT and CTL assays revealed that the two modified epitopes-induced
CTLs had a higher functional avidity and produced stronger cytotoxicity to lyse constitutively
HDAg-expressing Hep-G2 cells. Interestingly, the spectrums of the T cell receptor
(TCR) cross-reactivity are broadened and response to multiple HDV variants by the
enhanced epitopes immunization.
Conclusions
The modified HDV peptides can enhance the immunogenicity and the induced CTLs can
cross-react with multiple HDV variants. Combination with the two enhanced epitopes
might be a potential immunotherapeutic agent to control HDV quasispecies in HLA-A2
chronic hepatitis D patients.
Abbreviations:
CTLs (cytotoxic T lymphocytes), HDV (hepatitis delta virus), HDAg (hepatitis delta antigen), HBV (hepatitis B virus), HCC (hepatocellular carcinoma), HLA (human leukocyte antigen), PCR (polymerase chain reaction), TCR (T cell receptor)Keywords
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Article info
Publication history
Published online: February 17, 2009
Accepted:
November 23,
2008
Received in revised form:
November 7,
2008
Received:
September 24,
2008
Associate Editor: V. BarnabaFootnotes
☆The authors declare that they do not have anything to disclose regarding funding from industries or conflict of interest with respect to this manuscript.
Identification
Copyright
© 2009 European Association for the Study of the Liver. Published by Elsevier Inc. All rights reserved.
