HBV DNA vaccine with adjuvant cytokines induced specific immune responses against HBV infection

• Published in: World journal of gastroenterology : WJG 2003-01, Vol.9 (1), p.108-111
• Main Authors: Du, De-Wei, Jia, Zhan-Sheng, Li, Guang-Yu, Zhou, Yong-Ying
• Format: Article
• Language: English
• Subjects: Adjuvants, Immunologic; Animals; Cytotoxicity, Immunologic; Genetic Vectors; Hepatitis B - immunology; Hepatitis B - prevention & control; Hepatitis B - therapy; Hepatitis B Antibodies - blood; Hepatitis B Surface Antigens - immunology; Hepatitis B Vaccines - immunology; Hepatitis B virus - genetics; Hepatitis B virus - immunology; Humans; Interleukin-12 - genetics; Interleukin-12 - immunology; Interleukin-2 - genetics; Interleukin-2 - immunology; Interleukins - genetics; Interleukins - immunology; Mice; Mice, Inbred BALB C; Neoplasm Transplantation; Plasmids; Tumor Cells, Cultured; Vaccines, DNA - immunology; Viral Hepatitis
• ISSN: 1007-9327; 2219-2840
• DOI: 10.3748/wjg.v9.i1.108

To seek for an effective method to improve the immune responses induced by DNA vaccine expressing HBV surface antigen (pCR3.1-S) in Balb/c mice (H-2(d)). The pCR3.1-S plasmid and the eukaryotic expression vectors expressing murine IL-2 (pDOR-IL-2) or IL-12 (pWRG3169) were injected into mice subcutaneously. The immune responses to pCR3.1-S and the adjuvant effect of the cytokines plasmid were studied. Meanwhile the effect of pCR3.1-S on anti-translated subcutaneous tumor of P815 mastocytoma cells stably expressing HBsAg (P815-HBV-S) was also studied. Anti-HBs in serum was detected by enzyme-linked immunoadsorbent assay (ELISA) and HBsAg specific cytotoxic T lymphocytes (CTLs) activity was measured by (51)Cr release assay. After three weeks of DNA immunization, the cells of P815-HBV-S were inoculated into mice subcutaneously and the tumor growth was measured every five days. The survival rate and living periods of mice were also calculated. After 8 wk DNA immunization, the A 450 nm values of sera in mice immunized with pCR3.1, pCR3.1-S and pCR3.1-S codeliveried with IL-2 or IL-12 plasmids were 0.03+/-0.01, 1.24+/-0.10, 1.98+/-0.17 and 1.67+/-0.12 respectively. Data in mice codeliveried pCR3.1-S with IL-2 or IL-12 plasmids were significantly higher than that of mice injected pCR3.1 or pCR3.1-S only. The HBsAg specific CTL activities in mice coinjected with pCR3.1-S and IL-2 or IL-12 eukaryotic expression vectors were (61.9+/-7.1) % and (73.3+/-8.8) %, which were significantly higher than that of mice injected with pCR3.1 (10.1+/-2.1) % or pCR3.1-S (50.5 +/-6.4) %. The HBsAg specific CTL activities in mice injected with pCR3.1, pCR3.1-S, pCR3.1-S combined with IL-2 or IL-12 eukaryotic expression vectors decreased significantly to (3.2+/-0.8) %, (10.6+/-1.4) %, (13.6+/-1.3) % and (16.9+/-2.3) % respectively after the spleen cells were treated by anti-CD8(+) monoclonal antibody, but presented no significant change to anti-CD4(+) monoclonal antibody or unrelated to monoclonal antibody. The HBV-S DNA vaccine (pCR3.1-S) could evidently inhibit the tumor growth, prolong the survival period of mice and improve the survival rate of mice and these effects could be improved by IL-12 gene codeliveried. HBV DNA vaccine has a strong antigenicity in humoral and cellular immunities, which can be promoted by plasmid expressing IL-2 or IL-12. CD8+ cells executed the CTL activities. DNA vaccine may be useful for both prophylaxis and treatment of HBV infection.