Engineering enhancement of the immune response to HBV DNA vaccine in mice by the use of LIGHT gene adjuvant.
DNA vaccines could induce protective immune responses in several animal models. Many strategies have been employed to improve the effect of nucleic acid vaccines. LIGHT is a member of the TNF superfamily and functions as a co-stimulatory molecule for T cell proliferation. In the study, the immunogenicity in the induction of humoral and cellular immune responses by HBV DNA vaccine and the adjuvant effect of LIGHT were studied in a murine model. The eukaryotic expression plasmid pcDNA-L was constructed by inserting mouse LIGHT gene into the vector pcDNA3.1(+). In vitro expression of LIGHT was detected by RT-PCR and indirect immunofluorescence assay in transfected HeLa cells. MLR assay showed that LIGHT-transfected DCs induced markedly higher allogeneic lymphocyte proliferation than pcDNA-transfected DCs and untreated DCs at all dilutions. After BALB/c mice were immunized by three intramuscular injections of the HBV DNA vaccine plasmids alone or in combination with LIGHT expression plasmids, the different levels of anti-HBV immune responses were measured comparable to the control groups immunized with parent plasmid pcDNA or PBS. The HBsAg-specific splenocytes proliferation and specific cytotoxic activities of splenic CTLs in the coinoculation group were both significantly higher than those in the HBV DNA single inoculation group, and an enhancement of antibody response was also observed in the coinoculation group compared with the single inoculation group. Taken together, coimmunization of HBV DNA vaccine plasmids and LIGHT expression plasmids can elicit stronger humoral and cellular immune responses in mice than HBV DNA vaccine plasmids alone, and LIGHT may be an effective immunological adjuvant in HBV DNA vaccination.
Zhang
Yali
Y
School of Life Science, East China Normal University, Shanghai 200062, People's Republic of China.
Jiang
Wenzheng
W
Fan
Yan
Y
Wen
Jiejun
J
Hao
Wenli
W
Qian
Min
M
D000276:Adjuvants, Immunologic; D000818:Animals; D005260:Female; D005822:Genetic Vectors; D006367:HeLa Cells; D006509:Hepatitis B / Q000276:immunology* / Q000517:prevention & control; D006510:Hepatitis B Antibodies / Q000097:blood; D006514:Hepatitis B Surface Antigens / Q000276:immunology; D017325:Hepatitis B Vaccines / Q000008:administration & dosage / Q000235:genetics / Q000276:immunology; D006801:Humans; D007114:Immunization; D008213:Lymphocyte Activation; D051379:Mice; D008807:Mice, Inbred BALB C; D010957:Plasmids / Q000008:administration & dosage / Q000235:genetics / Q000276:immunology; D013154:Spleen / Q000276:immunology; D013602:T-Lymphocytes, Cytotoxic / Q000276:immunology; D053326:Tumor Necrosis Factor Ligand Superfamily Member 14 / Q000008:administration & dosage / Q000235:genetics / Q000276:immunology; D019444:Vaccines, DNA / Q000008:administration & dosage / Q000235:genetics / Q000276:immunology*
D000276:Adjuvants, Immunologic; D006510:Hepatitis B Antibodies; D006514:Hepatitis B Surface Antigens; D017325:Hepatitis B Vaccines; C505915:Tnfsf14 protein, mouse; D053326:Tumor Necrosis Factor Ligand Superfamily Member 14; D019444:Vaccines, DNA