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Infection and Immunity, September 1998, p. 4193-4202, Vol. 66, No. 9
0019-9567/98/$04.00+0
Copyright © 1998, American Society for Microbiology. All rights reserved.

Simultaneous Induction of Multiple Antigen-Specific Cytotoxic T Lymphocytes in Nonhuman Primates by Immunization with a Mixture of Four Plasmodium falciparum DNA Plasmids

Ruobing Wang,1,2 Denise L. Doolan,1,dagger Yupin Charoenvit,1 Richard C. Hedstrom,1 Malcolm J. Gardner,1,Dagger Peter Hobart,3 John Tine,4 Martha Sedegah,1,5 Victoria Fallarme,1,2 John B. Sacci Jr.,1,5 Manjit Kaur,1 Dennis M. Klinman,6 Stephen L. Hoffman,1 and Walter R. Weiss1,*

Malaria Program, Naval Medical Research Institute, Bethesda, Maryland 208891; Henry M. Jackson Foundation, Rockville, Maryland 208522; Vical Incorporated, San Diego, California 921213; Virogenetics Corporation, Troy, New York 121804; Department of Microbiology and Immunology, University of Maryland, Baltimore, Maryland 212015; and Section of Retroviral Immunology, Center for Biologics Evaluation and Research, Food and Drug Administration, Bethesda, Maryland 208926

Received 9 February 1998/Returned for modification 10 April 1998/Accepted 4 June 1998

CD8+ T cells have been implicated as critical effector cells in protective immunity against malaria parasites developing within hepatocytes. A vaccine that protects against malaria by inducing CD8+ T cells will probably have to include multiple epitopes on the same protein or different proteins, because of parasite polymorphism and genetic restriction of T-cell responses. To determine if CD8+ T-cell responses against multiple P. falciparum proteins can be induced in primates by immunization with plasmid DNA, rhesus monkeys were immunized intramuscularly with a mixture of DNA plasmids encoding four P. falciparum proteins or with individual plasmids. All six monkeys immunized with PfCSP DNA, seven of nine immunized with PfSSP2 DNA, and five of six immunized with PfExp-1 or PfLSA-1 DNA had detectable antigen-specific cytotoxic T lymphocytes (CTL) after in vitro restimulation of peripheral blood mononuclear cells. CTL activity was genetically restricted and dependent on CD8+ T cells. By providing the first evidence for primates that immunization with a mixture of DNA plasmids induces CD8+ T-cell responses against all the components of the mixture, these studies provide the foundation for multigene immunization of humans.

* Corresponding author. Mailing address: Malaria Program, Naval Medical Research Institute, 12300 Washington Ave., Rockville, MD 20852. Phone: (301) 295-1705. Fax: (301) 295-6171. E-mail: weissw{at}nmripo.nmri.nnmc.navy.mil.

dagger Present address: Queensland Institute Medical Research, Queensland, Australia.

Dagger Present address: The Institute for Genomic Research, Rockville, MD.

Infection and Immunity, September 1998, p. 4193-4202, Vol. 66, No. 9
0019-9567/98/$04.00+0
Copyright © 1998, American Society for Microbiology. All rights reserved.


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Copyright © 1998 by the American Society for Microbiology. All rights reserved.