Enhanced immune responses using plasmid DNA replicon vaccine encoding the Hc domain of Clostridium botulinum neurotoxin serotype A.
In current study, the immunogenicity of a plasmid DNA replicon vaccine (pSCARSHc) encoding the Hc domain of Clostridium botulinum neurotoxin serotype A (AHc) was investigated and compared with a conventional plasmid DNA vaccine (pcDNASHc) encoding the same antigen. In vitro, pSCARSHc incorporating Semliki Forest virus (SFV) replicon could express AHc protein and induce apoptosis of transfected cells. Comparison with the conventional plasmid DNA vaccine (pcDNASHc) yielded several interesting results. First, our self-designed pSCARSHc could induce relatively higher AHc-specific antibodies and lymphocyte proliferative responses in immunized Balb/c mice, especially at low doses. Second, while both pSCARSHc and pcDNASHc induced Th2-type immune responses, the ratio of IgG1 to IgG2a was lower in pSCARSHc groups and the Th2- and Th1-type humoral immune responses induced by pSCARSHc were also stronger than that of the pcDNASHc vaccine. Third, it was shown that the sera from pSCARSHc-vaccinated mice conferred more efficient protection than those from pcDNASHc-vaccinated mice by BoNT/A neutralization assay. Finally, mice immunized with pSCARSHc could also elicit more efficient protection against BoNT/A than pcDNASHc. These results indicate that our plasmid DNA replicon vaccine can provide strong immunogenicity and should be a potential alternative strategy to conventional DNA vaccines in developing an efficacious vaccine against C. botulinum neurotoxin serotype A.
Yu
Yun-Zhou
YZ
Beijing Institute of Biotechnology, 20 Dong Dajie Street, Fengtai District, Beijing 100071, China.
Zhang
Shu-Ming
SM
Sun
Zhi-Wei
ZW
Wang
Shuang
S
Yu
Wei-Yuan
WY
D000818:Animals; D000907:Antibodies, Bacterial / Q000097:blood; D001428:Bacterial Vaccines / Q000235:genetics / Q000276:immunology*; D019274:Botulinum Toxins, Type A / Q000737:chemistry / Q000235:genetics / Q000276:immunology*; D001906:Botulism / Q000276:immunology / Q000517:prevention & control*; D049109:Cell Proliferation; D003014:Clostridium botulinum / Q000235:genetics / Q000276:immunology*; D005260:Female; D007074:Immunoglobulin G / Q000097:blood; D008213:Lymphocyte Activation; D051379:Mice; D008807:Mice, Inbred BALB C; D010957:Plasmids / Q000235:genetics; D017434:Protein Structure, Tertiary; D012672:Semliki forest virus / Q000235:genetics; D016019:Survival Analysis; D013601:T-Lymphocytes / Q000276:immunology; D018417:Th1 Cells / Q000145:classification; D018418:Th2 Cells / Q000276:immunology; D019444:Vaccines, DNA / Q000235:genetics / Q000276:immunology*
D000907:Antibodies, Bacterial; D001428:Bacterial Vaccines; D007074:Immunoglobulin G; D019444:Vaccines, DNA; D019274:Botulinum Toxins, Type A