title: 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.
abstract: 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.
authors.affiliation: Malaria Program, Naval Medical Research Center, Bethesda, Maryland 20814-5055, USA. charoenvity@nmripo.mnri.navy.mil
authors.forename: Y
authors.initials: Y
authors.lastname: Charoenvit
authors.forename: V F
authors.initials: VF
authors.lastname: Majam
authors.forename: G
authors.initials: G
authors.lastname: Corradin
authors.forename: J B
authors.initials: JB
authors.lastname: Sacci
authors.forename: R
authors.initials: R
authors.lastname: Wang
authors.forename: D L
authors.initials: DL
authors.lastname: Doolan
authors.forename: T R
authors.initials: TR
authors.lastname: Jones
authors.forename: E
authors.initials: E
authors.lastname: Abot
authors.forename: M E
authors.initials: ME
authors.lastname: Patarroyo
authors.forename: F
authors.initials: F
authors.lastname: Guzman
authors.forename: S L
authors.initials: SL
authors.lastname: Hoffman
mesh_terms: D000595:Amino Acid Sequence; D000818:Animals; D000913:Antibodies, Protozoan / Q000097:blood; D000953:Antigens, Protozoan / Q000276:immunology*; D015496:CD4-Positive T-Lymphocytes / Q000276:immunology*; D018604:Epitope Mapping; D005260:Female; D007114:Immunization; D007132:Immunoglobulin Isotypes / Q000097:blood; D007371:Interferon-gamma / Q000502:physiology*; D008288:Malaria / Q000517:prevention & control*; D017780:Malaria Vaccines / Q000276:immunology*; D051379:Mice; D008807:Mice, Inbred BALB C; D008810:Mice, Inbred C57BL; D008969:Molecular Sequence Data; D010967:Plasmodium yoelii / Q000276:immunology*; D015800:Protozoan Proteins / Q000276:immunology*
chemical_list: D000913:Antibodies, Protozoan; D000953:Antigens, Protozoan; C100626:HEP17 protein, Plasmodium falciparum; D007132:Immunoglobulin Isotypes; D017780:Malaria Vaccines; D015800:Protozoan Proteins; D007371:Interferon-gamma