Cytotoxic T cell responses against hepatitis B virus polymerase induced by genetic immunization.
OBJECTIVE
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-2d) 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.
zu Putlitz
J
J
Molecular Hepatology Laboratory, Massachusetts General Hospital Cancer Center and Harvard Medical School, Boston, USA.
Encke
J
J
Wands
J R
JR
D016475:3T3 Cells; D000818:Animals; D000917:Antibody Formation; D002857:Chromium / Q000378:metabolism; D005260:Female; D015684:Gene Products, pol / Q000276:immunology*; D018014:Gene Transfer Techniques; D005822:Genetic Vectors; D006515:Hepatitis B virus / Q000201:enzymology*; D007114:Immunization / Q000379:methods*; D051379:Mice; D008807:Mice, Inbred BALB C; D013602:T-Lymphocytes, Cytotoxic / Q000276:immunology*; D014616:Vaccinia virus / Q000235:genetics
D015684:Gene Products, pol; C066027:P protein, Hepatitis B virus; D002857:Chromium