title: Variable effects of the co-administration of a GM-CSF-expressing plasmid on the immune response to flavivirus DNA vaccines in mice.
abstract: As a cytokine adjuvant, granulocyte-macrophage colony-stimulating factor (GM-CSF) has been demonstrated to play central roles in the enhancement of the immune response and protection elicited by experimental vaccines. However, in our previous work, the co-administration of GM-CSF produced untoward effects on the immune response induced by a Japanese encephalitis virus DNA vaccine candidate. This study aimed to elucidate the adjuvant roles of GM-CSF in several Flaviviridae virus DNA vaccine candidates. Our results showed that the effects of GM-CSF were diverse: co-inoculated GM-CSF caused significant suppression to the dengue virus type 1 and type 2 prM-E DNA vaccinations and influenced protective efficiency against virus challenge. In contrast, GM-CSF showed little effect or an enhancement on the immune response elicited by hepatitis C virus C or E1 DNA vaccine candidates. Notably, these effects of GM-CSF were highly durable. Our results suggested that the adjuvant roles of the GM-CSF plasmid were complex and diverse, ranging from enhancement to suppression, depending on the immunogen of Flaviviridae virus DNA vaccine candidates. Therefore, the application of GM-CSF as a vaccine adjuvant or a therapeutic agent should be evaluated carefully.
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.affiliation: Department of Microbiology, School of Basic Medical Sciences, Capital Medical University, Beijing, People's Republic of China.
authors.forename: Na
authors.initials: N
authors.lastname: Gao
authors.affiliation: Department of Microbiology, School of Basic Medical Sciences, Capital Medical University, Beijing, People's Republic of China.
authors.forename: Jiangman
authors.initials: J
authors.lastname: Wu
authors.affiliation: Department of Microbiology, School of Basic Medical Sciences, Capital Medical University, Beijing, People's Republic of China.
authors.forename: Xiaoyan
authors.initials: X
authors.lastname: Zheng
authors.affiliation: Department of Microbiology, School of Basic Medical Sciences, Capital Medical University, Beijing, People's Republic of China.
authors.forename: Jieqiong
authors.initials: J
authors.lastname: Li
authors.affiliation: Department of Microbiology, School of Basic Medical Sciences, Capital Medical University, Beijing, People's Republic of China.
authors.forename: Dongying
authors.initials: D
authors.lastname: Fan
authors.affiliation: Department of Microbiology, School of Basic Medical Sciences, Capital Medical University, Beijing, People's Republic of China; Center of Epilepsy, Beijing Institute for Brain Disorders, People's Republic of China. Electronic address: anjing60@aliyun.com.
authors.forename: Jing
authors.initials: J
authors.lastname: An
mesh_terms: D000276:Adjuvants, Immunologic; D000818:Animals; D057134:Antibodies, Neutralizing / Q000097:blood / Q000276:immunology; D000914:Antibodies, Viral / Q000097:blood / Q000276:immunology; D045744:Cell Line, Tumor; D004195:Disease Models, Animal; D005260:Female; D005416:Flavivirus / Q000235:genetics / Q000276:immunology*; D018177:Flavivirus Infections / Q000276:immunology* / Q000401:mortality / Q000517:prevention & control*; D016178:Granulocyte-Macrophage Colony-Stimulating Factor / Q000235:genetics* / Q000276:immunology*; D016174:Hepacivirus / Q000276:immunology; D006801:Humans; D007114:Immunization; D056747:Immunomodulation; D051379:Mice; D009500:Neutralization Tests; D010957:Plasmids / Q000008:administration & dosage / Q000235:genetics; D019444:Vaccines, DNA / Q000008:administration & dosage / Q000235:genetics / Q000276:immunology*; D014765:Viral Vaccines / Q000008:administration & dosage / Q000235:genetics / Q000276:immunology*
chemical_list: D000276:Adjuvants, Immunologic; D057134:Antibodies, Neutralizing; D000914:Antibodies, Viral; D019444:Vaccines, DNA; D014765:Viral Vaccines; D016178:Granulocyte-Macrophage Colony-Stimulating Factor
keywords: DNA vaccine; Dengue virus; Flaviviridae virus; Granulocyte-macrophage colony-stimulating factor; Hepatitis C virus