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Enhanced responses to a DNA vaccine encoding a fusion antigen that is directed to sites of immune induction

Nature volume 392, pages 408–411 (1998)Cite this article

Abstract

Viral infection and vaccination with DNA both induce similar immune responses to encoded antigens that are produced by the host1,2. The availability of antigens in lymphoid organs is important in generating an immune response to viral challenge3. Antigen availability may also be important in the response to DNA vaccines, because immune responses are stronger when antigen is secreted from DNA-transfected cells4,5. We directed antigen to lymphoid organs by vaccination with DNA encoding antigen–ligand fusion proteins. The two ligands examined bind to receptors that are present on high endothelial venule cells of lymph nodes or on antigen-presenting cells. Here we show that both the humoral and the cellular immune responses to a model DNA vaccine were enhanced using either antigen-targeting strategy. Moreover, directing antigen to antigen-presenting cells speeded up, and altered the form of, the immune response. Directing antigen to sites of immune-response induction may represent a generic means of tailoring a potent and effective immune response to a DNA vaccine.

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Figure 1: Secretion and dimer formation of human IgG (hIg) and fusion molecules from transfected NIT cells.
Figure 2: Immune responses to DNA-encoded antigen in BALB/c mice.
Figure 3: Influence of CTLA4Ig on the antibody response after immunization with DNA or protein.

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Acknowledgements

We thank J. F. A. P. Miller and L. C. Harrison for help in preparing this manuscript, and W. R. Heath, R. M. Sutherland, D. M. Tarlinton, D. Drew and R. Strugnell for helpful discussions. This work was supported by NH and MRC of Australia, Appel Estate, Diabetes Australia and a JDFI-NIH grant.

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Authors and Affiliations

  1. Autoimmunity and Transplantation Division, Walter and Eliza Hall Institute of Medical Research, Melbourne, 3050, Victoria, Australia

    J. S. Boyle, J. L. Brady & A. M. Lew

  2. Co-operative Research Centre for Vaccine Technology, Queensland Institute of Medical Research, Brisbane, 4029, Queensland, Australia

    A. M. Lew

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  1. J. S. Boyle
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Correspondence to A. M. Lew.

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Boyle, J., Brady, J. & Lew, A. Enhanced responses to a DNA vaccine encoding a fusion antigen that is directed to sites of immune induction. Nature 392, 408–411 (1998). https://doi.org/10.1038/32932

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