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Infection and Immunity, November 1999, p. 5604-5614, Vol. 67, No. 11
0019-9567/99/$04.00+0
Copyright © 1999, American Society for Microbiology. All rights reserved.
CD4+ T-Cell- and Gamma
Interferon-Dependent Protection against Murine Malaria by Immunization
with Linear Synthetic Peptides from a Plasmodium yoelii
17-Kilodalton Hepatocyte Erythrocyte Protein
Yupin
Charoenvit,1,*
Victoria Fallarme
Majam,1,2
Giampietro
Corradin,3
John B.
Sacci Jr.,1,4
Ruobing
Wang,1,2
Denise L.
Doolan,1,5
Trevor R.
Jones,1
Esteban
Abot,1,2
Manuel E.
Patarroyo,6
Fanny
Guzman,6 and
Stephen
L.
Hoffman1
Malaria Program, Naval Medical Research
Center, Bethesda, Maryland 20814-50551;
Henry M. Jackson Foundation, Rockville, Maryland
208522; Institute of Biochemistry,
University of Lausanne, Epalinges, Switzerland3;
Department of Microbiology and Immunology, University of
Maryland School of Medicine, Baltimore, Maryland
212014; Pan American Health
Organization, Regional Office of the World Health Organization,
Washington, DC 200375; and Instituto de
Immunologia, Hospital San Juan de Dios, Universidad Nacional de
Colombia, Bogota, Colombia6
Received 17 March 1999/Returned for modification 1 June
1999/Accepted 9 August 1999
Most work on protective immunity against the pre-erythrocytic
stages of malaria has focused on induction of antibodies that prevent
sporozoite invasion of hepatocytes, and CD8+ T-cell
responses that eliminate infected hepatocytes. We recently reported
that immunization of A/J mice with an 18-amino-acid synthetic linear
peptide from Plasmodium yoelii sporozoite surface protein 2 (SSP2) in TiterMax adjuvant induces sterile protection that is
dependent on CD4+ T cells and gamma interferon (IFN-
).
We now report that immunization of inbred A/J mice and outbred CD1 mice
with each of two linear synthetic peptides from the 17-kDa P. yoelii hepatocyte erythrocyte protein (HEP17) in the same
adjuvant also induces protection against sporozoite challenge that is
dependent on CD4+ T cells and IFN-
. The SSP2 peptide and
the two HEP17 peptides are recognized by B cells as well as T cells,
and the protection induced by these peptides appears to be directed
against the infected hepatocytes. In contrast to the peptide-induced
protection, immunization of eight different strains of mice with
radiation-attenuated sporozoites induces protection that is absolutely
dependent on CD8+ T cells. Data represented here
demonstrate that CD4+ T-cell-dependent protection can be
induced by immunization with linear synthetic peptides. These studies
therefore provide the foundation for an approach to
pre-erythrocytic-stage malaria vaccine development, based on the
induction of protective CD4+ T-cell responses, which will
complement efforts to induce protective antibody and CD8+
T-cell responses.
*
Corresponding author. Mailing address: Malaria Program,
Naval Medical Research Center, 12300 Washington Ave., Rockville, MD 20852. Phone: (301) 295-1177. Fax: (301) 295-6171. E-mail:
charoenvity{at}nmripo.nmri.nnmc.navy.mil.
Infection and Immunity, November 1999, p. 5604-5614, Vol. 67, No. 11
0019-9567/99/$04.00+0
Copyright © 1999, American Society for Microbiology. All rights reserved.
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