title: Enhanced potency of replicon vaccine using one vector to simultaneously co-express antigen and interleukin-4 molecular adjuvant.
abstract: We evaluated the utility of interleukin-4 (IL-4) as molecular adjuvant of replicon vaccines for botulinum neurotoxin serotype A (BoNT/A) in mouse model. In both Balb/c and C57/BL6 mice that received the plasmid DNA replicon vaccines derived from Semliki Forest virus (SFV) encoding the Hc gene of BoNT/A (AHc), the immunogenicity was significantly modulated and enhanced by co-delivery or co-express of the IL-4 molecular adjuvant. The enhanced potencies were also produced by co-delivery or co-expression of the IL-4 molecular adjuvant in mice immunized with the recombinant SFV replicon particles (VRP) vaccines. In particular, when AHc and IL-4 were co-expressed within the same replicon vaccine vector using dual-expression or bicistronic IRES, the anti-AHc antibody titers, serum neutralization titers and survival rates of immunized mice after challenged with BoNT/A were significantly increased. These results indicate IL-4 is an effective Th2-type adjuvant for the replicon vaccines in both strain mice, and the co-expression replicon vaccines described here may be an excellent candidate for further vaccine development in other animals or humans. Thus, we described a strategy to design and develop efficient vaccines against BoNT/A or other pathogens using one replicon vector to simultaneously co-express antigen and molecular adjuvant.
authors.affiliation: College of Life Science and Bioengineering; Beijing Jiaotong University; Beijing, PR China.
authors.forename: Yao
authors.initials: Y
authors.lastname: Ma
authors.forename: Huai-Jie
authors.initials: HJ
authors.lastname: An
authors.forename: Xiao-Qi
authors.initials: XQ
authors.lastname: Wei
authors.forename: Qing
authors.initials: Q
authors.lastname: Xu
authors.forename: Yun-Zhou
authors.initials: YZ
authors.lastname: Yu
authors.forename: Zhi-Wei
authors.initials: ZW
authors.lastname: Sun
mesh_terms: D000276:Adjuvants, Immunologic / Q000235:genetics / Q000378:metabolism*; D000818:Animals; D057134:Antibodies, Neutralizing / Q000097:blood; D000992:Antitoxins / Q000097:blood; D019274:Botulinum Toxins, Type A / Q000235:genetics / Q000276:immunology*; D001906:Botulism / Q000517:prevention & control*; D004195:Disease Models, Animal; D005822:Genetic Vectors; D015847:Interleukin-4 / Q000235:genetics / Q000378:metabolism*; D008807:Mice, Inbred BALB C; D008810:Mice, Inbred C57BL; D010957:Plasmids; D012093:Replicon; D012672:Semliki forest virus / Q000235:genetics; D016019:Survival Analysis; D064166:Vaccine Potency; D019444:Vaccines, DNA / Q000008:administration & dosage / Q000235:genetics / Q000276:immunology*; D014614:Vaccines, Synthetic / Q000008:administration & dosage / Q000235:genetics / Q000276:immunology
chemical_list: D000276:Adjuvants, Immunologic; D057134:Antibodies, Neutralizing; D000992:Antitoxins; D019444:Vaccines, DNA; D014614:Vaccines, Synthetic; D015847:Interleukin-4; D019274:Botulinum Toxins, Type A
keywords: botulinum neurotoxin serotype A; co-expression; interleukin-4; molecular adjuvant; replicon vaccine