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Modulation of amplitude and direction of in vivo immune responses by co-administration of cytokine gene expression cassettes with DNA immunogens.

Publication ,  Journal Article
Kim, JJ; Trivedi, NN; Nottingham, LK; Morrison, L; Tsai, A; Hu, Y; Mahalingam, S; Dang, K; Ahn, L; Doyle, NK; Wilson, DM; Chattergoon, MA ...
Published in: Eur J Immunol
March 1998

Immunization with nucleic acids has been shown to induce both antigen-specific cellular and humoral immune responses in vivo. We hypothesize that immunization with DNA could be enhanced by directing specific immune responses induced by the vaccine based on the differential correlates of protection known for a particular pathogen. Recently we and others reported that specific immune responses generated by DNA vaccine could be modulated by co-delivery of gene expression cassettes encoding for IL-12, granulocyte-macrophage colony-stimulating factor and the co-stimulatory molecule CD86. To further engineer the immune response in vivo, we investigated the induction and regulation of immune responses following the co-delivery of pro-inflammatory cytokine (IL-1 alpha, TNF-alpha, and TNF-beta), Th1 cytokine (IL-2, IL-12, IL-15, and IL-18), and Th2 cytokine (IL-4, IL-5 and IL-10) genes. We observed enhancement of antigen-specific humoral response with the co-delivery of Th2 cytokine genes IL-4, IL-5, and IL-10 as well as those of IL-2 and IL-18. A dramatic increase in antigen-specific T helper cell proliferation was seen with IL-2 and TNF-alpha gene co-injections. In addition, we observed a significant enhancement of the cytotoxic response with the co-administration of TNF-alpha and IL-15 genes with HIV-1 DNA immunogens. These increases in CTL response were both MHC class I restricted and CD8+ T cell dependent. Together with earlier reports on the utility of co-immunizing using immunologically important molecules together with DNA immunogens, we demonstrate the potential of this strategy as an important tool for the development of more rationally designed vaccines.

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Published In

Eur J Immunol

DOI

ISSN

0014-2980

Publication Date

March 1998

Volume

28

Issue

3

Start / End Page

1089 / 1103

Location

Germany

Related Subject Headings

  • Vaccines, DNA
  • Th2 Cells
  • Th1 Cells
  • T-Lymphocytes, Helper-Inducer
  • T-Lymphocytes, Cytotoxic
  • Mice, Inbred BALB C
  • Mice
  • Immunology
  • HIV Antibodies
  • Gene Expression
 

Citation

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Kim, J. J., Trivedi, N. N., Nottingham, L. K., Morrison, L., Tsai, A., Hu, Y., … Weiner, D. B. (1998). Modulation of amplitude and direction of in vivo immune responses by co-administration of cytokine gene expression cassettes with DNA immunogens. Eur J Immunol, 28(3), 1089–1103. https://doi.org/10.1002/(SICI)1521-4141(199803)28:03<1089::AID-IMMU1089>3.0.CO;2-L
Kim, J. J., N. N. Trivedi, L. K. Nottingham, L. Morrison, A. Tsai, Y. Hu, S. Mahalingam, et al. “Modulation of amplitude and direction of in vivo immune responses by co-administration of cytokine gene expression cassettes with DNA immunogens.Eur J Immunol 28, no. 3 (March 1998): 1089–1103. https://doi.org/10.1002/(SICI)1521-4141(199803)28:03<1089::AID-IMMU1089>3.0.CO;2-L.
Kim JJ, Trivedi NN, Nottingham LK, Morrison L, Tsai A, Hu Y, et al. Modulation of amplitude and direction of in vivo immune responses by co-administration of cytokine gene expression cassettes with DNA immunogens. Eur J Immunol. 1998 Mar;28(3):1089–103.
Kim, J. J., et al. “Modulation of amplitude and direction of in vivo immune responses by co-administration of cytokine gene expression cassettes with DNA immunogens.Eur J Immunol, vol. 28, no. 3, Mar. 1998, pp. 1089–103. Pubmed, doi:10.1002/(SICI)1521-4141(199803)28:03<1089::AID-IMMU1089>3.0.CO;2-L.
Kim JJ, Trivedi NN, Nottingham LK, Morrison L, Tsai A, Hu Y, Mahalingam S, Dang K, Ahn L, Doyle NK, Wilson DM, Chattergoon MA, Chalian AA, Boyer JD, Agadjanyan MG, Weiner DB. Modulation of amplitude and direction of in vivo immune responses by co-administration of cytokine gene expression cassettes with DNA immunogens. Eur J Immunol. 1998 Mar;28(3):1089–1103.
Journal cover image

Published In

Eur J Immunol

DOI

ISSN

0014-2980

Publication Date

March 1998

Volume

28

Issue

3

Start / End Page

1089 / 1103

Location

Germany

Related Subject Headings

  • Vaccines, DNA
  • Th2 Cells
  • Th1 Cells
  • T-Lymphocytes, Helper-Inducer
  • T-Lymphocytes, Cytotoxic
  • Mice, Inbred BALB C
  • Mice
  • Immunology
  • HIV Antibodies
  • Gene Expression