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

Gao, Na; Chen, Wei; Zheng, Qun; Fan, Dongying; Zhang, Junlei; Chen, Hui; Gao, George F.; Zhou, Dujin; An, Jing

doi:10.1016/j.imlet.2009.12.023

Cited by 23 publications

(15 citation statements)

References 38 publications

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“…Humoral immune response is responsible for protecting animals from the JEV challenge [25]. HI and PRNT antibody titers were measured in pigs inoculated with the inactivated JEV vaccine in presence or absence of reporGM-CSF protein.…”

Section: Discussionmentioning

confidence: 99%

Inactivated genotype 1 Japanese encephalitis vaccine for swine

Yang

Nah

Kim

et al. 2014

Clin Exp Vaccine Res

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PurposeJapanese encephalitis is a reproductive disorder caused by Japanese encephalitis virus (JEV) in swine. Recent genotype (G) shift phenomenon (G3 to G1) in the Asia-wide has posed a challenge for proper prevention by the current vaccine strain. Thus, new kinds of JEV G1 vaccines with enhanced immunogenicity have been required for pigs.Materials and MethodsRecombinant porcine granulocyte monocyte-colony stimulating factor (reporGM-CSF) protein was expressed in Spodoptera frugiperda (Sf-9) cells using baculovirus expression system. Two kinds of trials with inactivated JEV vaccines containing IMS1313 adjuvant (Seppic, France) were prepared with or without reporGM-CSF protein. Safety and immunogenicity of the pigs inoculated with the JEV vaccines via intramuscular route was evaluated for 28 days after inoculation.ResultsMice, guinea pigs, and fattening pigs inoculated with the inactivated vaccine showed no signs for 14 and 21 days. Both hemagglutination inhibition and plaque reduction neutralizing antibody titers were significantly higher in pigs immunized with the vaccine containing reporGM-CSF protein after boosting. However, on the side of vaccine efficacy, most mice (87%) immunized with the inactivated JEV vaccine survived after virulent JEV challenge. Whereas the group with the vaccine containing reporGM-CSF protein showed lower protective effects than the vaccine alone for the biological activity of the GM-CSF depending on species specific.ConclusionOur data indicate that animals inoculated with the JEV vaccines was safe and pigs inoculated with inactivated JEV vaccine containing reporGM-CSF protein showed higher humoral immune responses than that of inactivated JEV vaccine without reporGM-CSF protein.

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Section: Discussionmentioning

confidence: 99%

Inactivated genotype 1 Japanese encephalitis vaccine for swine

Yang

Nah

Kim

et al. 2014

Clin Exp Vaccine Res

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“…Plasmid construction. The fragments of HBV preS, e, c and x, obtained by PCR from the pHBV1.2 (complete genome of HBV isolate 57-1 subtype adw, a kind gift by Professor Lai Wei, Peking University, and the GenBank accession number AY518556.1) (18) respectively, were subcloned into the efficient vector, pCAGGSP7, containing the β-actin promoter (19). The positive clones were named pHBV-S, pHBV-E, pHBV-C and pHBV-X, respectively.…”

Section: Methodsmentioning

confidence: 99%

HBV promotes the proliferation of hepatic stellate cells via the PDGF-B/PDGFR-β signaling pathway in vitro

Bai

et al. 2012

International Journal of Molecular Medicine

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The activation of hepatic stellate cells (HSCs) is closely associated with liver fibrosis in chronic hepatitis B virus (HBV) infection. However, the molecular mechanisms leading to HSC activation remain unclear. It has been reported that the platelet-derived growth factor-B (PDGF-B)/PDGF receptor-β (PDGFR-β) signaling pathway is involved in this process. Thus, we investigated whether HBV and its protein contribute to HSC proliferation by the PDGF-B/PDGFR-β signaling pathway. HBV particles were purified from the supernatant of HepG2.2.15 cells by ultracentrifugation and the cell lines carrying HBV preS, e, c or x genes were obtained. After incubation with HBV particles or co-cultured with the cell lines expressed in the viral protein, the proliferation of LX-2 cells, an HSC cell line, were detected by flow cyto-metry and real-time PCR and the expression of molecules related to the PDGF-B/PDGFR-β signaling pathway were further measured. Our results indicated that HBV particles, c and x proteins promoted LX-2 proliferation and increased the mRNA levels of PDGF-B, PDGFR-β, collagen-I and α-smooth muscle actin (α-SMA), as well as the phosphorylation of PDGFR-β; however, the expression protein levels of PDGF-B and PDGFR-β remained unchanged. In conclusion, HBV particles and HBV c and x proteins promote HSC proliferation and fibrogenesis in vitro and the PDGF-B/PDGFR-β signaling pathway is important in this process.

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“…In addition, as a well-recognized regulator of hematopoiesis, GM-CSF is commonly administered in clinical practice to treat neutropenia and enhance leukocyte activity. However, our recent study of a JEV DNA vaccine [10] showed that co-inoculation of the GM-CSF plasmid significantly suppressed the specific IgG response and resulted in decreased protection against JEV challenge. These data raise the concern that the use of GM-CSF as an adjuvant or as a treatment agent might be harmful because GM-CSF can impair the vaccine-induced or anti-tumor immune responses under conditions that remain unclear.…”

Section: Discussionmentioning

confidence: 98%

“…The pCAG-GM plasmid encoding the murine GM-CSF fragment was constructed following a previously described protocol [10]. All gene sequences were obtained from GenBank Database (http://www.ncbi.nlm.nih.gov/genbank).…”

Section: Methodsmentioning

confidence: 99%

“…However, as an adjuvant, various roles of GM-CSF have been reported: it appeared to help generate an immune response in some studies but had no effect or even an inhibitory effect in others. For example, in our recent study on a Japanese encephalitis virus (JEV) DNA vaccine, we unexpectedly found that co-injection of the GM-CSF plasmid significantly suppressed the specific IgG response and led to decreased protection against JEV challenge [10]. Similarly, a suppressive effect of the GM-CSF plasmid was also observed by a study of a human immunodeficiency virus (HIV) DNA vaccine, in which high levels of type I IFN at the local inoculation site involved in this process were discovered [11].…”

Section: Introductionmentioning

confidence: 99%

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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

Chen¹,

Gao²,

Fan³

et al. 2012

PLoS ONE

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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.

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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

Cited by 23 publications

References 38 publications

Inactivated genotype 1 Japanese encephalitis vaccine for swine

Inactivated genotype 1 Japanese encephalitis vaccine for swine

HBV promotes the proliferation of hepatic stellate cells via the PDGF-B/PDGFR-β signaling pathway in vitro

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

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