Immune response induced by immunization with Hepatitis B virus core DNA isolated from chronic active hepatitis patients

Abstract

There are many mutations in the gene encoding Hepatitis B virus (HBV) core antigen of chronic active hepatitis patients, and such mutations are most likely to be related to the severity of disease. Here, we constructed plasmids containing wild-type and deletion type of HBV core gene (HBc) to develop an experimental DNA vaccine and to compare immunogenicity of two types of HBc vaccine. Twenty-nine wild-types and seven deletion types of HBc were detected in sera of 32 Korean patients with chronic active hepatitis. Four wild-types (W1, W2, W4, W6) and two deletion types (D3, D4) of HBc were cloned into the pcDNA3 vector. Intramuscular immunization with wild-type HBc efficiently increased serum anti-HBc antibody response in a dose-dependent manner. Anti-HBc antibody response in mice injected with W6 increased 14 days after immunization, and peaked after 30 days and was maintained at least up to 50 days. W6 immunization induced a specific cytotoxic T lymphocyte response to W6-transfected 3LL (3LL-W6), and reduced the sizes of tumor mass of mice challenged with 3LL-W6 or 3LL transfected with D4. However, intramuscular immunization with D3 and D4 did not show antibody response at all. D3 and D4 have 157 bp (from 331 to 491 bp) and 122 bp (from 327 to 448 bp) gene deletion, respectively, and these encode class II MHC-restricted T-cell epitope. Altogether, these results suggest that mutant virus that has deleted HBc gene may evade immune systems due to loss of T-cell epitope. © 2001 Elsevier Science B.V. All rights reserved. Keywords: Hepatitis B virus; Core gene; DNA vaccine; CTL (cytotoxic T lymphocyte)