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

Jong J. Kim, Neil N. Trivedi, Liesl K. Nottingham, Lake Morrison, Anthony Tsai, Yin Hu, Sundarasamy Mahalingam, Kesen Dang, Lois Ahn, Nicole K. Doyle, Darren M. Wilson, Michael A. Chattergoon, Ara A. Chalian, Jean D. Boyer, Michael G. Agadjanyan, David B. Weiner

Research output: Contribution to journalArticlepeer-review

Abstract

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-1α, TNF-α, and TNF-β), 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-α gene co-injections. In addition, we observed a significant enhancement of the cytotoxic response with the co-administration of TNF-α 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.

Original languageEnglish (US)
Pages (from-to)1089-1103
Number of pages15
JournalEuropean Journal of Immunology
Volume28
Issue number3
DOIs
StatePublished - Mar 1998
Externally publishedYes

Keywords

  • AIDS
  • Cytokine
  • DNA vaccination
  • HIV-1
  • Immune response

ASJC Scopus subject areas

  • Immunology and Allergy
  • Immunology

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