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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-gamma ). 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-gamma . 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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Copyright © 1999 by the American Society for Microbiology. All rights reserved.