Effect of plasmid backbone modification by different human CpG motifs on the immunogenicity of DNA vaccine vectors.

Download
2005-09-01
Coban, C
Ishii, KJ
Gürsel, Mayda
Klinman, DM
Kumar, N
DNA vaccines, in general, have been found to be poorly immunogenic in nonhuman primates and humans as compared with mice. As the immunogenicity of DNA plasmids relies, to a large extent, on the presence of CpG motifs as built in adjuvants, we addressed the issue of poor immunogenicity by inserting recently identified CpG oligonucleotides (ODN) optimal for human (K-type or D-type CpG ODN) into the backbone of plasmid VR1020. We found that plasmid DNA containing K-type CpG motifs or D-type CpG motifs significantly enhanced the up-regulation of surface molecules and production of interleukin-6 from human peripheral blood mononuclear cells (PBMC) and stimulated monocytes to develop into functionally mature dendritic cells (DC) compared with unmodified plasmid. Monocyte maturation into DC was through plasmacytoid DC present in the culture. It is interesting that the K-type CpG motif-modified plasmid stimulated significant levels of interferon (IFN)-gamma and IFN-alpha from human PBMC. Immunization of mice with D-type CpG motif-modified plasmid, encoding Plasmodium falciparum surface protein 25, yielded enhanced antigen-specific antibodies. Taken together, these results suggest that insertion of immunomodulatory human CpG motifs into plasmid DNA can improve immunogenicity of DNA vaccines.
Journal of leukocyte biology

Suggestions

Influence of STRO-1 selection on osteogenic potential of human tooth germ derived mesenchymal stem cells
Ercal, Pinar; Pekozer, Gorke G.; Gumru, Osman Z.; KÖSE, GAMZE; Ramazanoglu, Mustafa (Elsevier BV, 2017-10-01)
Mesenchymal stem cells derived from the human tooth germ (hTGSCs) are a heterogeneous cell population that can differentiate into osteogenic, neurogenic, and adipogenic lineages. The aim of this study was to compare the osteogenic differentiation capacity of STRO-1 positive (STRO-1 +) hTGSCs and unsorted heterogeneous hTGSCs and to establish if STRO-1 + cells are more committed to osteogenic differentiation. HTGSCs were isolated from impacted third molar tooth germ tissues of adolescents, and a subpopulatio...
Effect of suppressive DNA on CpG-induced immune activation.
Yamada, H; Gursel, I; Takeshita, F; Conover, J; Ishii, KJ; Gürsel, Mayda; Takeshita, S; Klinman, DM (The American Association of Immunologists, 2002-11-15)
Bacterial DNA and synthetic oligodeoxynucleotides (ODN) containing unmethylated CpG motifs stimulate a strong innate immune response. This stimulation can be abrogated by either removing the CpG DNA or adding inhibitory/suppressive motifs. Suppression is dominant over stimulation and is specific for CpG-induced immune responses (having no effect on LPS- or Con A-induced activation). Individual cells noncompetitively internalize both stimulatory and suppressive ODN. Studies using ODN composed of both stimula...
Effect of FMD vaccination schedule of dams on the level and duration of maternally derived antibodies
Sareyyupoglu, B.; Gulyaz, V.; Cokcaliskan, C.; Unal, Y.; Cokulgen, T.; Uzunlu, E.; Gurcan, S.; İlk Dağ, Özlem (Elsevier BV, 2019-11-01)
Vaccination against Foot and Mouth Disease (FMD) in pregnant cows is crucial to produce greater immunity in new born calves, especially in late gestation, as this directly affects neonatal immunity. Therefore, we aimed to investigate how late gestation FMD vaccination of pregnant cows affects the maternally derived antibodies in their offspring. Pregnant cows were vaccinated with and without booster vaccination during the 3rd months (early gestation vaccination, EGV) or the 6.5th months (late gestation vacc...
Plasmacytoid Dendritic Cell Response to CpG ODN Correlates with CXCL16 Expression and Is Inhibited by ox-LDL
Gürsel, Mayda; GÜRSEL, İHSAN (Hindawi Limited, 2013-01-01)
Structurally distinct classes of synthetic CpG oligonucleotides (ODN) differentially activate human immune cells. K-type ODN trigger plasmacytoid dendritic cells (pDCs) to differentiate and produce TNF alpha. In contrast, D-type ODN stimulate large amounts of IFN alpha secretion from pDCs. The cell-surface receptor CXCL16 was previously shown to influence the nature and specificity of CpG ODN-induced immune activation. Here, we evaluated the expression and function of CXCL16 on pDC from healthy volunteers. ...
Effect of scaffold architecture and BMP-2/BMP-7 delivery on in vitro bone regeneration
Yilgor, Pinar; Sousa, Rui A.; Reis, Rui L.; Hasırcı, Nesrin; Hasırcı, Vasıf Nejat (2010-11-01)
The aim of this study was to develop 3-D tissue engineered constructs that mimic the in vivo conditions through a self-contained growth factor delivery system. A set of nanoparticles providing the release of BMP-2 initially followed by the release of BMP-7 were incorporated in poly(epsilon-caprolactone) scaffolds with different 3-D architectures produced by 3-D plotting and wet spinning. The release patterns were: each growth factor alone, simultaneous, and sequential. The orientation of the fibers did not ...
Citation Formats
C. Coban, K. Ishii, M. Gürsel, D. Klinman, and N. Kumar, “Effect of plasmid backbone modification by different human CpG motifs on the immunogenicity of DNA vaccine vectors.,” Journal of leukocyte biology, pp. 647–55, 2005, Accessed: 00, 2020. [Online]. Available: https://hdl.handle.net/11511/49218.