title: Enhanced efficacy of DNA vaccination against botulinum neurotoxin serotype A by co-administration of plasmids encoding DC-stimulating Flt3L and MIP-3α cytokines.
abstract: Targeting antigens encoded by DNA vaccines to the key antigen-presenting cells by chemotactic or growth factors, is an effective strategy for enhancing the potency of DNA vaccinations. Here, we report the effects of chemotactic or growth factors on a DNA vaccine against botulinum neurotoxin serotype A (BoNT/A) in a mouse model. We demonstrated that mice immunized with DNA constructs encoding the Hc domain of BoNT/A (AHc) fused with DC-stimulating Flt3L or MIP-3α cytokines failed to elicit an enhanced or efficacious AHc-specific humoral or protective response in mice. However, the potency of DNA vaccination was significantly modulated and enhanced by co-administration of AHc-expressing DNA with pFlt3L or pMIP-3α, which generated strong immune and protective responses against BoNT/A. Moreover, the enhanced potency was further boosted by co-administration of AHc-expressing DNA with the combination of pFlt3L and pMIP-3α in mice, but not with the Flt3L-MIP-3α fusion molecule, which indicated that co-immunization with both pFlt3L and pMIP-3α could synergistically enhance AHc-specific immune and protective responses against BoNT/A. In summary, our findings indicate that co-administration of plasmids encoding antigen and cytokine rather than administration of plasmids encoding cytokine-antigen fusion is effective to enhance the potency of AHc-expressing DNA vaccine.
authors.affiliation: Institute of Life Science and Biotechnology, Beijing Jiaotong University, 3 Shangyuan Residence, Haidian District, Beijing 100044, China. Electronic address: qingxu@bjtu.edu.cn.
authors.forename: Qing
authors.initials: Q
authors.lastname: Xu
authors.affiliation: Laboratory Animal Research Center, Nanfang Hospital Southern Medical University, Guangzhou 510515, China.
authors.forename: Yu-Feng
authors.initials: YF
authors.lastname: Zhu
authors.affiliation: Institute of Life Science and Biotechnology, Beijing Jiaotong University, 3 Shangyuan Residence, Haidian District, Beijing 100044, China; Beijing Institute of Biotechnology, 20 Dongdajie Street, Fengtai District, Beijing 100071, China.
authors.forename: Hai-Chao
authors.initials: HC
authors.lastname: Wang
authors.affiliation: Beijing Institute of Biotechnology, 20 Dongdajie Street, Fengtai District, Beijing 100071, China.
authors.forename: Zheng-Wei
authors.initials: ZW
authors.lastname: Gong
authors.affiliation: Beijing Institute of Biotechnology, 20 Dongdajie Street, Fengtai District, Beijing 100071, China. Electronic address: yunzhouyu@163.com.
authors.forename: Yun-Zhou
authors.initials: YZ
authors.lastname: Yu
mesh_terms: D000818:Animals; D019274:Botulinum Toxins, Type A / Q000276:immunology*; D054418:Chemokine CCL20 / Q000276:immunology / Q000494:pharmacology*; D003713:Dendritic Cells; D005260:Female; D007117:Immunization, Secondary; D008565:Membrane Proteins / Q000276:immunology / Q000494:pharmacology*; D051379:Mice; D008807:Mice, Inbred BALB C; D010957:Plasmids / Q000276:immunology / Q000494:pharmacology*; D019444:Vaccines, DNA / Q000276:immunology / Q000494:pharmacology*
chemical_list: D054418:Chemokine CCL20; D008565:Membrane Proteins; D019444:Vaccines, DNA; C084881:flt3 ligand protein; D019274:Botulinum Toxins, Type A
keywords: Co-administration; DC; DNA vaccine; Flt3L; MIP-3α; Molecular adjuvant