Cellular and humoral immune response to hepatitis B virus structural proteins in mice after DNA-based immunization

BACKGROUND & AIMS: 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 hepatiti...

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Published in:	Gastroenterology (New York, N.Y. 1943) Vol. 112; no. 4; pp. 1307 - 1320
Main Authors:	Geissler, M, Tokushige, K, Chante, CC, Zurawski, VR, Wands, JR
Format:	Journal Article
Language:	English
Published:	New York, NY Elsevier Inc 01-04-1997 Elsevier
Subjects:	Animals Antibody Formation Biological and medical sciences Cell Division Cytokines - metabolism DNA, Viral - immunology Epidemiology. Vaccinations Female General aspects Hepatitis B Core Antigens - analysis Hepatitis B Surface Antigens - analysis Hepatitis B virus - metabolism Immunity, Cellular Immunization Infectious diseases Medical sciences Mice Mice, Inbred BALB C Mice, Inbred C57BL T-Lymphocytes - cytology T-Lymphocytes - metabolism T-Lymphocytes, Cytotoxic - physiology Viral Envelope Proteins - immunology Vaccination Rodentia Hepatic disease Cellular immunity Experimental study Infection Virus Viral hepatitis B Proteins Immunoprophylaxis Vertebrata Mammalia Mouse Hepadnaviridae Viral disease Animal DNA Digestive diseases Biological effect Hepatitis B virus Virus envelope Humoral immunity
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Summary:	BACKGROUND & AIMS: 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. (Gastroenterology 1997 Apr;112(4):1307-20)
Bibliography:	ObjectType-Article-1 SourceType-Scholarly Journals-1 ObjectType-Feature-2 content type line 23
ISSN:	0016-5085 1528-0012
DOI:	10.1016/S0016-5085(97)70145-8