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Abstract:

PyNTTTTGT oligodeoxinucleotides (ODNs) cause activation, proliferation and immunoglobulin secretion on B cells, and the expression of co-stimulatory molecules on plasmacytoid dendritic cells of primates. It has now been discovered that these ODNs are also active on rat cells. This fact allowed us to investigate the adjuvant properties of PyNTTTTGT ODNs in a human Hepatitis B vaccine using this animal model. A very significant increment, as compared with the antigen alone, was observed in the antibody production induced by vaccination with the recombinant Hepatitis B surface antigen adjuvated with the PyNTTTTGT prototype IMT504 ODN. Analysis of the IgG subclass distribution in the sera of vaccinated animals indicated that, although an increase was observed in the titer of all the IgG subclasses, the increase on the Th1-associated IgG2b subclass was clearly more pronounced. Remarkably, this effect on the IgG2b titer was observed even if alum, a Th2 promoting adjuvant, was present together with IMT504 in the vaccine formulation. The increase in the Th1 response induced by IMT504 was also suggested by in vitro gamma interferon secretion assays. Monkeys of the species Cebus apella immunized with the recombinant Hepatitis B surface antigen plus alum and IMT504 also showed titers of antibodies against the antigen several times superior to the titers observed in control animals immunized with the antigen plus alum without ODN. Since rat and monkey cells are significantly less immunostimulated "in vitro" by PyNTTTTGT ODNs than human cells, the present results reasonably predict a very good performance of these ODNs as adjuvants in human vaccination. © 2005 Elsevier Ltd. All rights reserved.

Registro:

Documento: Artículo
Título:PyNTTTTGT prototype oligonucleotide IMT504 is a potent adjuvant for the recombinant Hepatitis B vaccine that enhances the Th1 response
Autor:Elias, F.; Flo, J.; Rodriguez, J.M.; De Nichilo, A.; Lopez, R.A.; Zorzopulos, J.; Nagle, C.; Lahoz, M.; Montaner, A.
Filiación:Depto. de Quím. Biol., Fac. de Ciencias Exactas Y Naturales, Cuidad Universitaria, Buenos Aires (1428), Argentina
Immunotech S.A, Florida 1, Buenos Aires (1440), Argentina
Inst. de Invest. Biomédicas, Fund. Pablo Cassará, Saladillo 2452, Buenos Aires (1440), Argentina
Ctro. Educacion Medica Invest. C., Galvan 4102, Buenos Aires (1431), Argentina
Palabras clave:Immunostimulatory oligonucleotide; Th1 answer; Vaccine adjuvant; aluminum potassium sulfate; gamma interferon; hepatitis B antigen; immunoglobulin G2b; immunological adjuvant; imt 504; oligonucleotide; recombinant hepatitis B vaccine; unclassified drug; animal cell; animal experiment; animal tissue; antibody production; antibody titer; antigen antibody reaction; article; B lymphocyte; bioassay; cell secretion; cellular immunity; controlled study; cytokine release; drug potency; female; Hepatitis B virus; immune response; immunoglobulin production; immunostimulation; in vitro study; monkey; nonhuman; physical chemistry; priority journal; rat; Th1 cell; Th2 cell; vaccination; vaccine production
Año:2005
Volumen:23
Número:27
Página de inicio:3597
Página de fin:3603
DOI: http://dx.doi.org/10.1016/j.vaccine.2004.12.030
Título revista:Vaccine
Título revista abreviado:Vaccine
ISSN:0264410X
CODEN:VACCD
CAS:aluminum potassium sulfate, 10043-67-1; gamma interferon, 82115-62-6
Registro:https://bibliotecadigital.exactas.uba.ar/collection/paper/document/paper_0264410X_v23_n27_p3597_Elias

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Citas:

---------- APA ----------
Elias, F., Flo, J., Rodriguez, J.M., De Nichilo, A., Lopez, R.A., Zorzopulos, J., Nagle, C.,..., Montaner, A. (2005) . PyNTTTTGT prototype oligonucleotide IMT504 is a potent adjuvant for the recombinant Hepatitis B vaccine that enhances the Th1 response. Vaccine, 23(27), 3597-3603.
http://dx.doi.org/10.1016/j.vaccine.2004.12.030
---------- CHICAGO ----------
Elias, F., Flo, J., Rodriguez, J.M., De Nichilo, A., Lopez, R.A., Zorzopulos, J., et al. "PyNTTTTGT prototype oligonucleotide IMT504 is a potent adjuvant for the recombinant Hepatitis B vaccine that enhances the Th1 response" . Vaccine 23, no. 27 (2005) : 3597-3603.
http://dx.doi.org/10.1016/j.vaccine.2004.12.030
---------- MLA ----------
Elias, F., Flo, J., Rodriguez, J.M., De Nichilo, A., Lopez, R.A., Zorzopulos, J., et al. "PyNTTTTGT prototype oligonucleotide IMT504 is a potent adjuvant for the recombinant Hepatitis B vaccine that enhances the Th1 response" . Vaccine, vol. 23, no. 27, 2005, pp. 3597-3603.
http://dx.doi.org/10.1016/j.vaccine.2004.12.030
---------- VANCOUVER ----------
Elias, F., Flo, J., Rodriguez, J.M., De Nichilo, A., Lopez, R.A., Zorzopulos, J., et al. PyNTTTTGT prototype oligonucleotide IMT504 is a potent adjuvant for the recombinant Hepatitis B vaccine that enhances the Th1 response. Vaccine. 2005;23(27):3597-3603.
http://dx.doi.org/10.1016/j.vaccine.2004.12.030