Cellular and humoral immune response to hepatitis B virus structural proteins in mice after DNA-based immunization.
OBJECTIVE
Development of a broad-based cellular immune response to hepatitis B viral structural proteins may be important for recovery from infection, and lack of such responses may lead to persistent viral infection and chronic liver disease. Strategies designed to enhance the hepatitis B virus (HBV)-specific immune response may be able to reduce persistent viral infection of the liver. The aim of this study was to induce HBV-specific cellular and humoral immune responses in mice using DNA-based immunizations with the large and middle envelope and nucleocapsid proteins.


METHODS
Antibodies to HBV structural proteins, T-helper-cell proliferation, and cytokine release and generation of cytotoxic T lymphocyte (CTL) activity were measured in vaccinated mice.


RESULTS
Immunized mice developed high-titer antibodies against envelope and core proteins in serum. More importantly, 93% of the immunized mice produced strong inflammatory CD4+ T-cell and CD8+ CTL responses to viral proteins.


CONCLUSIONS
This study shows that DNA-based vaccination will generate broad-based CTL activity as well as strong T-helper cell responses with the production of TH1-type cytokines to HBV structural proteins. Such constructs are promising candidates as antiviral agents, and these studies have defined some of the most immunogenic antigens for an immunotherapeutic approach of chronic HBV infection.
Geissler
M
M
Molecular Hepatology Laboratory, Massachusetts General Hospital, Charlestown 02129, USA.
Tokushige
K
K
Chante
C C
CC
Zurawski
V R
VR
Wands
J R
JR
D000818:Animals; D000917:Antibody Formation; D002455:Cell Division; D016207:Cytokines / Q000378:metabolism; D004279:DNA, Viral / Q000276:immunology*; D005260:Female; D006512:Hepatitis B Core Antigens / Q000032:analysis; D006514:Hepatitis B Surface Antigens / Q000032:analysis; D006515:Hepatitis B virus / Q000378:metabolism*; D007111:Immunity, Cellular; D007114:Immunization; D051379:Mice; D008807:Mice, Inbred BALB C; D008810:Mice, Inbred C57BL; D013601:T-Lymphocytes / Q000166:cytology / Q000378:metabolism; D013602:T-Lymphocytes, Cytotoxic / Q000502:physiology; D014759:Viral Envelope Proteins / Q000276:immunology*
D016207:Cytokines; D004279:DNA, Viral; D006512:Hepatitis B Core Antigens; D006514:Hepatitis B Surface Antigens; D014759:Viral Envelope Proteins