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Abstract:

Nucleic acid immunization is a new vaccination technology. DNA vaccines do not only carry the genetic information for the antigen of interest but also deliver an adjuvant effect due to the presence of immunostimulatory sequences within the plasmid backbone. It is generally assumed that the adjuvant properties of plasmid DNA are equal to those described for oligodeoxynucleotides (ODN) containing immunostimulatory CpG motifs. To challenge this hypothesis we have carried out a series of experiments comparing the ability of single- and double-stranded ODN containing CpG motifs to induce the activation of mouse spleen cells. Moreover, we compared the immunostimulatory properties of plasmids that were modified by the addition of two to four CpG motifs. Our results establish that plasmid DNA express their adjuvanticity as either double or single strands, and no differences were observed between modified and unmodified plasmids. On the other hand, the strongest stimulatory ODN sequences lost their adjuvant properties when administered as double-strand DNA. Furthermore, the profile of cytokines induced on spleen cells by plasmid DNA and ODN is different. Strikingly, plasmid DNA induces a moderate synthesis of IL-6 and a strong synthesis of IFN-γ, whereas stimulation with ODN showed an inverse profile with a higher increase in the synthesis of IL-6 but a moderate increase in IFN-γ. Finally, in vivo studies were consistent with the results obtained in vitro. Mice immunized with modified or unmodified plasmids encoding the glycoprotein D of HSV showed similar levels of cellular and humoral immune responses.

Registro:

Documento: Artículo
Título:Immunostimulatory effects of plasmid DNA and synthetic oligodeoxynucleotides
Autor:Zelenay, S.; Elías, F.; Fló, J.
Filiación:Laboratorio de Inmunoquimica, Departamento de Quimica Biologica, Universidad de Buenos Aires, Pabellón 2, Piso 4to, 1428 Buenos Aires, Argentina
Instituto Gulbenkian de Ciencia, Oeiras, Portugal
Palabras clave:CpG motif; DNA vaccine; Immunoadjuvanticity; antigen; cytokine; DNA vaccine; gamma interferon; glycoprotein D; interleukin 6; oligodeoxynucleotide derivative; plasmid DNA; animal cell; article; B lymphocyte; cell activation; cell culture; cell proliferation; cellular immunity; controlled study; CpG island; cytokine production; DNA modification; DNA strand; drug mechanism; female; humoral immunity; immunization; immunostimulation; in vitro study; in vivo study; mouse; nonhuman; priority journal; protein motif; spleen cell; Adjuvants, Immunologic; Animals; Antigens, CD40; B-Lymphocytes; Cytokines; Dendritic Cells; Female; Interferon Type II; Killer Cells, Natural; Lymphocyte Activation; Mice; Mice, Inbred BALB C; Oligodeoxyribonucleotides; Plasmids; Thionucleotides; Vaccines, DNA; Viral Envelope Proteins
Año:2003
Volumen:33
Número:5
Página de inicio:1382
Página de fin:1392
DOI: http://dx.doi.org/10.1002/eji.200323614
Título revista:European Journal of Immunology
Título revista abreviado:Eur. J. Immunol.
ISSN:00142980
CODEN:EJIMA
CAS:gamma interferon, 82115-62-6; Adjuvants, Immunologic; Antigens, CD40; CPG-oligonucleotide; Cytokines; glycoprotein D-herpes simplex virus type 2; Interferon Type II, 82115-62-6; Oligodeoxyribonucleotides; Thionucleotides; Vaccines, DNA; Viral Envelope Proteins
Registro:https://bibliotecadigital.exactas.uba.ar/collection/paper/document/paper_00142980_v33_n5_p1382_Zelenay

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Citas:

---------- APA ----------
Zelenay, S., Elías, F. & Fló, J. (2003) . Immunostimulatory effects of plasmid DNA and synthetic oligodeoxynucleotides. European Journal of Immunology, 33(5), 1382-1392.
http://dx.doi.org/10.1002/eji.200323614
---------- CHICAGO ----------
Zelenay, S., Elías, F., Fló, J. "Immunostimulatory effects of plasmid DNA and synthetic oligodeoxynucleotides" . European Journal of Immunology 33, no. 5 (2003) : 1382-1392.
http://dx.doi.org/10.1002/eji.200323614
---------- MLA ----------
Zelenay, S., Elías, F., Fló, J. "Immunostimulatory effects of plasmid DNA and synthetic oligodeoxynucleotides" . European Journal of Immunology, vol. 33, no. 5, 2003, pp. 1382-1392.
http://dx.doi.org/10.1002/eji.200323614
---------- VANCOUVER ----------
Zelenay, S., Elías, F., Fló, J. Immunostimulatory effects of plasmid DNA and synthetic oligodeoxynucleotides. Eur. J. Immunol. 2003;33(5):1382-1392.
http://dx.doi.org/10.1002/eji.200323614