Co-expression of Japanese encephalitis virus prM-E-NS1 antigen with granulocyte-macrophage colony-stimulating factor enhances humoral and anti-virus immunity after DNA vaccination.
Japanese encephalitis virus (JEV) is an agent of Japanese encephalitis, and granulocyte-macrophage colony-stimulating factor (GM-CSF) is an attractive DNA vaccine adjuvant for its antigen presentation. In the present study, we have constructed DNA vaccines that carried JEV prM-E-NS1 genes with or without the GM-CSF gene. Immunization with the bicistronic plasmid pCAG-JEGM that co-expresses GM-CSF and viral prM-E-NS1, resulted in the highest IgG response and sufficient protection against virus-challenged BALB/c mice. However, much to our surprise, co-inoculation of the GM-CSF plasmid with the pCAG-JE plasmid expressing viral prM-E-NS1 lead to a low antibody titer and a relatively low survival rate. Moreover, anamnestic antibody-mediated protection played a dominant role in the mice JEV challenge model, according to the enhancement of post-challenge neutralizing antibody titers and further adoptive transfer experiments. Taken together, this study should encourage further development of JEV DNA vaccine strategies and caution against the use of cytokines as an adjuvant.
Gao
Na
N
Department of Histology and Embryology, Third Military Medical University, Chongqing 400038, PR China.
Chen
Wei
W
Zheng
Qun
Q
Fan
Dong-ying
DY
Zhang
Jun-lei
JL
Chen
Hui
H
Gao
George F
GF
Zhou
De-shan
DS
An
Jing
J
D019264:Adoptive Transfer; D000818:Animals; D000914:Antibodies, Viral / Q000008:administration & dosage / Q000097:blood; D002460:Cell Line; D003001:Cloning, Molecular; D003602:Cytotoxicity, Immunologic; D004664:Encephalitis Virus, Japanese / Q000235:genetics / Q000276:immunology* / Q000472:pathogenicity; D004672:Encephalitis, Japanese / Q000097:blood / Q000276:immunology*; D005260:Female; D016178:Granulocyte-Macrophage Colony-Stimulating Factor / Q000235:genetics / Q000276:immunology / Q000378:metabolism*; D006801:Humans; D056724:Immunity, Humoral; D051379:Mice; D008807:Mice, Inbred BALB C; D019444:Vaccines, DNA; D017361:Viral Nonstructural Proteins / Q000235:genetics / Q000276:immunology / Q000378:metabolism*
D000914:Antibodies, Viral; C100315:NS1 protein, Flavivirus; D019444:Vaccines, DNA; D017361:Viral Nonstructural Proteins; D016178:Granulocyte-Macrophage Colony-Stimulating Factor