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Infection and Immunity, September 1998, p. 4193-4202, Vol. 66, No. 9
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.
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


*
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.
Present address: Queensland Institute Medical Research, Queensland,
Australia.
Present address: The Institute for Genomic Research, Rockville,
MD.
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