title: Suppressive effects on the immune response and protective immunity to a JEV DNA vaccine by co-administration of a GM-CSF-expressing plasmid in mice.
abstract: As a potential cytokine adjuvant of DNA vaccines, granulocyte-macrophage colony-stimulating factor (GM-CSF) has received considerable attention due to its essential role in the recruitment of antigen-presenting cells, differentiation and maturation of dendritic cells. However, in our recent study of a Japanese encephalitis virus (JEV) DNA vaccine, co-inoculation of a GM-CSF plasmid dramatically suppressed the specific IgG response and resulted in decreased protection against JEV challenge. It is known that GM-CSF has been used in clinic to treat neutropenia for repopulating myeloid cells, and as an adjuvant in vaccine studies; it has shown various effects on the immune response. Therefore, in this study, we characterized the suppressive effects on the immune response to a JEV DNA vaccine by the co-administration of the GM-CSF-expressing plasmid and clarified the underlying mechanisms of the suppression in mice. Our results demonstrated that co-immunization with GM-CSF caused a substantial dampening of the vaccine-induced antibody responses. The suppressive effect was dose- and timing-dependent and likely related to the immunogenicity of the antigen. The suppression was associated with the induction of immature dendritic cells and the expansion of regulatory T cells but not myeloid-derived suppressor cells. Collectively, our findings not only provide valuable information for the application of GM-CSF in clinic and using as a vaccine adjuvant but also offer further insight into the understanding of the complex roles of GM-CSF.
authors.affiliation: Department of Microbiology, School of Basic Medical Sciences, Capital Medical University, Beijing, People's Republic of China.
authors.forename: Hui
authors.initials: H
authors.lastname: Chen
authors.forename: Na
authors.initials: N
authors.lastname: Gao
authors.forename: Dongying
authors.initials: D
authors.lastname: Fan
authors.forename: Jiangman
authors.initials: J
authors.lastname: Wu
authors.forename: Junping
authors.initials: J
authors.lastname: Zhu
authors.forename: Jieqiong
authors.initials: J
authors.lastname: Li
authors.forename: Juan
authors.initials: J
authors.lastname: Wang
authors.forename: Yanlei
authors.initials: Y
authors.lastname: Chen
authors.forename: Jing
authors.initials: J
authors.lastname: An
mesh_terms: D000276:Adjuvants, Immunologic / Q000008:administration & dosage / Q000009:adverse effects; D000818:Animals; D000914:Antibodies, Viral / Q000096:biosynthesis / Q000276:immunology; D049109:Cell Proliferation / Q000187:drug effects; D003713:Dendritic Cells / Q000187:drug effects / Q000276:immunology; D004664:Encephalitis Virus, Japanese / Q000187:drug effects / Q000276:immunology*; D004672:Encephalitis, Japanese / Q000276:immunology / Q000517:prevention & control* / Q000821:virology; D005260:Female; D016178:Granulocyte-Macrophage Colony-Stimulating Factor / Q000008:administration & dosage / Q000009:adverse effects* / Q000276:immunology; D056724:Immunity, Humoral / Q000187:drug effects* / Q000276:immunology; D051379:Mice; D008807:Mice, Inbred BALB C; D010957:Plasmids / Q000008:administration & dosage / Q000235:genetics / Q000276:immunology; D050378:T-Lymphocytes, Regulatory / Q000187:drug effects / Q000276:immunology; D019444:Vaccines, DNA / Q000008:administration & dosage* / Q000276:immunology; D014765:Viral Vaccines / Q000008:administration & dosage* / Q000276:immunology
chemical_list: D000276:Adjuvants, Immunologic; D000914:Antibodies, Viral; D019444:Vaccines, DNA; D014765:Viral Vaccines; D016178:Granulocyte-Macrophage Colony-Stimulating Factor