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Journal of Virology, August 2001, p. 7621-7628, Vol. 75, No. 16
0022-538X/01/$04.00+0   DOI: 10.1128/JVI.75.16.7621-7628.2001
Copyright © 2001, American Society for Microbiology. All rights reserved.

Induction of Potent Human Immunodeficiency Virus Type 1-Specific T-Cell-Restricted Immunity by Genetically Modified Dendritic Cells

Julianna Lisziewicz,1,* Dmitry I. Gabrilovich,2 Georg Varga,1,dagger Jianqing Xu,1 Philip D. Greenberg,3 Suresh K. Arya,4 Marnix Bosch,3 Jean-Paul Behr,5 and Franco Lori1

Research Institute for Genetic and Human Therapy (RIGHT), Washington, D.C. 200071; H. Lee Moffitt Cancer Center, University of South Florida, Tampa, Florida 336122; University of Washington Seattle, Seattle, Washington 981953; National Cancer Institute, National Institutes of Health, Bethesda, Maryland 208924; and Laboratoire de Chimie Génétique, Faculté de Pharmacie, 67401 Illkirch, France5

Received 26 January 2001/Accepted 14 May 2001

A novel technology combining replication- and integration-defective human immunodeficiency virus type 1 (HIV-1) vectors with genetically modified dendritic cells was developed in order to induce T-cell immunity. We introduced the vector into dendritic cells as a plasmid DNA using polyethylenimine as the gene delivery system, thereby circumventing the problem of obtaining viral vector expression in the absence of integration. Genetically modified dendritic cells (GMDC) presented viral epitopes efficiently, secreted interleukin 12, and primed both CD4+ and CD8+ HIV-specific T cells capable of producing gamma interferon and exerting potent HIV-1-specific cytotoxicity in vitro. In nonhuman primates, subcutaneously injected GMDC migrated into the draining lymph node at an unprecedentedly high rate and expressed the plasmid DNA. The animals presented a vigorous HIV-specific effector cytotoxic-T-lymphocyte (CTL) response as early as 3 weeks after a single immunization, which later developed into a memory CTL response. Interestingly, antibodies did not accompany these CTL responses, indicating that GMDC can induce a pure Th1 type of immune response. Successful induction of a broad and long-lasting HIV-specific cellular immunity is expected to control virus replication in infected individuals.

* Corresponding author. Mailing address: Research Institute for Genetic and Human Therapy (RIGHT), 2233 Wisconsin Ave., NW, Suite 503, Washington, DC 20007. Phone: (202) 687-2833. Fax: (202) 687-2907. E-mail: rightpv{at}tin.it.

dagger Present address: University of Muenster, 48149 Muenster, Germany.

Journal of Virology, August 2001, p. 7621-7628, Vol. 75, No. 16
0022-538X/01/$04.00+0   DOI: 10.1128/JVI.75.16.7621-7628.2001
Copyright © 2001, American Society for Microbiology. All rights reserved.


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