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Vaccine requirements for sustained cellular immunity to an intracellular parasitic infection

Nature Medicine volume 4, pages 1409–1415 (1998)Cite this article

Abstract

The humoral immunity induced by many viral and bacterial vaccines mediates protection that is maintained over a long period of time. In contrast, for other intracellular infections (such as with Leishmania major or Mycobacterium tuberculosis ) for which cell-mediated immunity is required for protection, the mechanisms for developing durable responses after vaccination have not been well defined. Here we demonstrate that vaccination with plasmid DNA encoding a specific leishmanial antigen is more effective than leishmanial protein plus recombinant IL-12 in eliciting long-term immunity capable of controlling L. major infection. We also show that leishmanial protein plus IL-12 DNA produces an immunity that lasts much longer than does immunity elicited by leishmanial protein plus IL-12 protein, indicating that the persistence of IL-12 may be the essential determinant in maintaining durable cell-mediated immune responses for an intracellular parasitic infection.

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Figure 1: LACK DNA provides effective memory immunity compared with that provided by LACK protein + rIL-12 protein.
Figure 2: Frequency of antigen-specific lymph node cells producing IFN-λ and IL-4 from vaccinated mice after infection.
Figure 3: ALM + IL-12 DNA provides effective memory immunity compared with that of ALM + rIL-12 protein.
Figure 4: Vaccination with LACK DNA and ALM + IL-12 DNA enhances the frequency of CD4+ cells producing IFN-λ after infection.

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Acknowledgements

We thank S. Reiner and W. Paul for advice and B.R. Marshall for editorial assistance.

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Author notes

  1. David L. Sacks: Laboratory of Parasitic Diseases, National Institute of Allergy and Infectious Diseases, National Institutes of Health, Bethesda, Maryland 20892, USA D.L.S. and R.A.S. contributed equally to this work

Authors and Affiliations

  1. National Institutes of Health, Bethesda , 20892, Maryland, USA

    Sanjay Gurunathan & Robert A. Seder

  2. Laboratory of Allergic Diseases, National Institute of Allergy and Infectious Diseases, National Institutes of Health, Bethesda, 20892, Maryland, USA

    Calman Prussin

Authors
  1. Sanjay Gurunathan
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Correspondence to Robert A. Seder.

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Gurunathan, S., Prussin, C., Sacks, D. et al. Vaccine requirements for sustained cellular immunity to an intracellular parasitic infection. Nat Med 4, 1409–1415 (1998). https://doi.org/10.1038/4000

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