title: A fusion DNA vaccine encoding middle version of HBV envelope protein fused to interleukin-21 did not enhance HBV-specific immune response in mice.
abstract: DNA vaccination can generate both humoral and cellular immunity, resulting in potential prophylactic and therapeutic vaccines in variety of conditions, including hepatitis B virus (HBV) infection. Fusion of cytokine gene is one of the ways to increase the immunogenicity of DNA vaccine. Interleukin (IL)-21 has been demonstrated to play an immunomodulatory role in HBV infection. Thus, we aimed to investigate the ability of IL-21 in the regulation of middle version of HBV envelop protein (MS) DNA vaccine. Fusion plasmid encoding IL-21 linked with MS was constructed. Normal and HBV transgenic mice were immunized by plasmid. pcDNA-IL-21/S2S induced a comparable level of anti-HBs antibody and HBsAg-specific CD8+ T-cell response with pcDNA-S2S. Furthermore, the level of circulating HBsAg was decreased by induction of anti-HBs antibody and HBsAg-specific CD8+ T-cell response to both pcDNA-IL-21/S2S and pcDNA-S2S vaccination in HBV transgenic mice. Thus, immunization with DNA vaccine encoding HBV MS protein induced both T- and B-cell response by targeting the specific antigen. Furthermore, it was also revealed that MS DNA vaccination could break immune tolerance in HBV transgenic mice. But IL-21 did not strengthen immune response induced by HBV DNA immunization. Our study suggested that MS-expressing plasmid may be useful for both preventive and therapeutic methods in HBV infection. However, IL-21 does not improve the immunogenicity and efficacy of MS DNA vaccination, and thus may not be used as a therapeutic marker for chronic hepatitis B.
authors.affiliation: 1 Center for Infectious Diseases, Tangdu Hospital, Fourth Military Medical University , Xi'an, China .
authors.forename: Ye
authors.initials: Y
authors.lastname: Zhang
authors.forename: Wen-Jing
authors.initials: WJ
authors.lastname: Su
authors.forename: Jue
authors.initials: J
authors.lastname: Wang
authors.forename: Xue-Fan
authors.initials: XF
authors.lastname: Bai
authors.forename: Chang-Xing
authors.initials: CX
authors.lastname: Huang
authors.forename: Jian-Qi
authors.initials: JQ
authors.lastname: Lian
mesh_terms: D000818:Animals; D018414:CD8-Positive T-Lymphocytes / Q000276:immunology; D006508:Hepatitis Antibodies / Q000097:blood; D006509:Hepatitis B / Q000517:prevention & control*; D017325:Hepatitis B Vaccines / Q000008:administration & dosage / Q000235:genetics / Q000276:immunology*; D007378:Interleukins / Q000235:genetics / Q000276:immunology*; D008297:Male; D008807:Mice, Inbred BALB C; D008822:Mice, Transgenic; D010957:Plasmids / Q000008:administration & dosage; D011993:Recombinant Fusion Proteins / Q000235:genetics / Q000276:immunology; D019444:Vaccines, DNA / Q000008:administration & dosage / Q000235:genetics / Q000276:immunology*; D014614:Vaccines, Synthetic / Q000008:administration & dosage / Q000235:genetics / Q000276:immunology; D014759:Viral Envelope Proteins / Q000235:genetics / Q000276:immunology*; D000098546:Interleukin-21
chemical_list: D006508:Hepatitis Antibodies; D017325:Hepatitis B Vaccines; D007378:Interleukins; D011993:Recombinant Fusion Proteins; D019444:Vaccines, DNA; D014614:Vaccines, Synthetic; D014759:Viral Envelope Proteins; C114312:middle envelope protein, Hepatitis B virus; D000098546:Interleukin-21