Cytotoxic T cell responses against hepatitis B virus polymerase induced by genetic immunization

Background/Aims: Individuals with chronic hepatitis B may benefit from genetic (DNA-based) immunization through induction of viral clearance by enhancement of suboptimal cellular immune responses. While marked cellular immune responses to hepatitis B virus (HBV) nucleocapsid and envelope proteins oc...

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Bibliographic Details
Published in:Journal of hepatology 2000-12, Vol.33 (6), p.986-991
Main Authors: Putlitz, Jasper zu, Encke, Jens, Wands, Jack R
Format: Article
Language:English
Subjects:
3T3 Cells
Animals
Antibody Formation
Chromium - metabolism
Cytotoxic T lymphocytes
ELISA
Female
Gene Products, pol - immunology
Gene Transfer Techniques
Genetic Vectors
Hepatitis
Hepatitis B virus - enzymology
Immunization - methods
Mice
Mice, Inbred BALB C
Polymerase
T-Lymphocytes, Cytotoxic - immunology
Vaccine
Vaccinia
Vaccinia virus - genetics
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Summary:Background/Aims: Individuals with chronic hepatitis B may benefit from genetic (DNA-based) immunization through induction of viral clearance by enhancement of suboptimal cellular immune responses. While marked cellular immune responses to hepatitis B virus (HBV) nucleocapsid and envelope proteins occur after genetic immunization in mice, it is unknown whether genetic immunization is capable of eliciting such responses to HBV polymerase. We wished to develop assays for the determination of HBV polymerase specific immune responses in mice and investigate whether genetic immunization may elicit humoral and cellular immune responses to HBV polymerase. Methods: BALB/c (H-2 d) mice were injected with a DNA expression construct for HBV polymerase. Humoral immune responses to HBV polymerase were analyzed with a newly established ELISA. Cellular immune responses were determined using recombinant vaccinia virus infected target cells expressing HBV polymerase at high levels. Results: Assays for the detection of HBV polymerase-specific immune responses were developed. Immunized animals exhibited substantial polymerase-specific cytotoxic T lymphocyte responses. However, no humoral immune responses to HBV polymerase were detectable. Conclusions: Our study demonstrates that DNA-based immunization will generate substantial CTL responses to HBV polymerase and may be an important component of an immunotherapeutic strategy to combat chronic HBV infection.
ISSN:0168-8278
1600-0641
DOI:10.1016/S0168-8278(00)80133-6