Induction of antibodies to the PreS region of surface antigens of woodchuck hepatitis virus (WHV) in chronic carrier woodchucks by immunizations with WHV surface antigens.
OBJECTIVE
One goal of therapeutic vaccinations against chronic hepatitis B virus infection is to stimulate the B-cell responses to viral surface antigens in chronic carriers. Here we investigated the induction of antibody responses to hepadnaviral surface antigens in the woodchuck model, with emphasis on the vaccination of woodchucks chronically infected with woodchuck hepatitis virus (WHV).


METHODS
Naive and chronically WHV-infected woodchucks were immunized with plasma-derived WHV surface antigens (p-WHsAg) containing the S and PreS sequences. Antibody responses to WHsAg and the WHV PreS region and viral load in immunized woodchucks were monitored.


RESULTS
After repeated immunizations with WHsAg, 17 of 18 chronic WHV carriers developed a persistent antibody response to WHsAg. These antibodies were mainly directed to epitopes within the PreS region and detectable by Western blotting. However, neither WHV DNA nor WHsAg concentrations in these woodchucks changed significantly by immunizations and during the follow up. Sequence analysis of WHV genomes showed that no WHV mutants emerged after the induction of anti-WHs/anti-WHpreS antibodies. No immunopathological changes in livers of immunized animals were recognized thus far.


CONCLUSIONS
Our study demonstrated that the immunological unresponsiveness of chronically WHV-infected woodchucks to WHsAg can be partially overcome by repeated immunizations with WHsAg.
Lu
Mengji
M
Institut für Virologie, Universitätsklinikum Essen, Hufelandstrasse 55, 45122 Essen, Germany. mengji.lu@uni-essen.de
Klaes
Ruediger
R
Menne
Stephan
S
Gerlich
Wolfram
W
Stahl
Benno
B
Dienes
Hans-Peter
HP
Drebber
Uta
U
Roggendorf
Michael
M
D000208:Acute Disease; D000818:Animals; D000917:Antibody Formation; D002353:Carrier State / Q000276:immunology*; D002908:Chronic Disease; D004279:DNA, Viral / Q000097:blood; D006509:Hepatitis B / Q000276:immunology / Q000473:pathology; D006510:Hepatitis B Antibodies / Q000276:immunology*; D006514:Hepatitis B Surface Antigens / Q000737:chemistry / Q000276:immunology*; D017919:Hepatitis B Virus, Woodchuck / Q000235:genetics / Q000276:immunology*; D007114:Immunization; D008099:Liver / Q000473:pathology; D008221:Lymphoid Tissue / Q000473:pathology; D008392:Marmota; D009994:Osmolar Concentration; D017434:Protein Structure, Tertiary; D014611:Vaccination
D004279:DNA, Viral; D006510:Hepatitis B Antibodies; D006514:Hepatitis B Surface Antigens