Dendritic cell (DC)-based anti-infective strategies: DCs engineered to secrete IL-12 are a potent vaccine in a murine model of an intracellular infection

Seema S. Ahuja, Robert L. Reddick, Naoko Sato, Elleanor Montalbo, Vannessa Kostecki, Weiguo Zhao, Matthew J. Dolan, Peter Melby, Sunil K. Ahuja

Research output: Contribution to journalArticle

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Abstract

Infections with intracellular pathogens such as Leishmania donovani and Mycobacterium tuberculosis pose serious health problems worldwide. Effective vaccines for these pathogens are not available. Furthermore, despite optimal therapy, disease progression is often seen with several intracellular infections. For these reasons, we initiated studies to develop novel anti- infective vaccine and treatment strategies that couple the potent Ag- presenting capacity of dendritic cells (DC) with paracrine delivery of potent anti-infective cytokines such as IL-12 to local immune response sites. We tested this strategy in a murine model of visceral leishmaniasis. Adoptive transfer of DCs pulsed ex vivo with soluble L. donovani Ags (SLDA) to naive mice induced the Ag-specific production of IFN-γ, and increased the percentage of activation markers on spleen lymphocytes. SLDA-pulsed DCs engineered by retroviral gene transfer techniques to secrete high levels of biologically active murine IL-12 augmented this immune response further. In several different vaccination and immunotherapy protocols, compared with sham-treated mice, animals receiving SLDA-pulsed DCs either before or following infection had 1-3 log lower parasite burdens, and this protection was associated with a pronounced enhancement in the parasite-specific IFN-γ response. The augmentation of this protection by IL-12-engineered DCs was striking. First, live parasites were not detected in the liver of mice vaccinated with IL-12-transduced, SLDA-pulsed DCs. Second, this parasitological response was associated with a nearly normal liver histology. In contrast, parasites and granulomas were found in mice vaccinated with SLDA-pulsed, nontransduced DCs. Collectively, these studies provide the rationale for the development of potent DC-based immunotherapies.

Original languageEnglish (US)
Pages (from-to)3890-3897
Number of pages8
JournalJournal of Immunology
Volume163
Issue number7
StatePublished - Oct 1 1999
Externally publishedYes

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Leishmania donovani
Interleukin-12
Dendritic Cells
Vaccines
Parasites
Infection
Immunotherapy
Gene Transfer Techniques
Visceral Leishmaniasis
Adoptive Transfer
Liver
Granuloma
Mycobacterium tuberculosis
Disease Progression
Histology
Vaccination
Spleen
Lymphocytes
Cytokines
Therapeutics

ASJC Scopus subject areas

  • Immunology

Cite this

Ahuja, S. S., Reddick, R. L., Sato, N., Montalbo, E., Kostecki, V., Zhao, W., ... Ahuja, S. K. (1999). Dendritic cell (DC)-based anti-infective strategies: DCs engineered to secrete IL-12 are a potent vaccine in a murine model of an intracellular infection. Journal of Immunology, 163(7), 3890-3897.

Dendritic cell (DC)-based anti-infective strategies : DCs engineered to secrete IL-12 are a potent vaccine in a murine model of an intracellular infection. / Ahuja, Seema S.; Reddick, Robert L.; Sato, Naoko; Montalbo, Elleanor; Kostecki, Vannessa; Zhao, Weiguo; Dolan, Matthew J.; Melby, Peter; Ahuja, Sunil K.

In: Journal of Immunology, Vol. 163, No. 7, 01.10.1999, p. 3890-3897.

Research output: Contribution to journalArticle

Ahuja, SS, Reddick, RL, Sato, N, Montalbo, E, Kostecki, V, Zhao, W, Dolan, MJ, Melby, P & Ahuja, SK 1999, 'Dendritic cell (DC)-based anti-infective strategies: DCs engineered to secrete IL-12 are a potent vaccine in a murine model of an intracellular infection', Journal of Immunology, vol. 163, no. 7, pp. 3890-3897.
Ahuja, Seema S. ; Reddick, Robert L. ; Sato, Naoko ; Montalbo, Elleanor ; Kostecki, Vannessa ; Zhao, Weiguo ; Dolan, Matthew J. ; Melby, Peter ; Ahuja, Sunil K. / Dendritic cell (DC)-based anti-infective strategies : DCs engineered to secrete IL-12 are a potent vaccine in a murine model of an intracellular infection. In: Journal of Immunology. 1999 ; Vol. 163, No. 7. pp. 3890-3897.
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