Induction of protective CTL responses against the Plasmodium yoelii circumsporozoite protein by immunization with peptides

J Immunol. 1997 Oct 1;159(7):3424-33.


To determine the optimum combination, concentration, and formulation of synthetic peptides and adjuvants to induce protective CTL responses against the Plasmodium yoelii circumsporozoite protein (PyCSP), BALB/c mice were immunized with linear and multiple antigen peptides (MAP) including PyCSP CTL and Th epitopes in Montanide's ISA51, Lipofectin, and Lipofectamine. An H-2K(d)-restricted PyCSP CTL epitope, SYVPSAEQI (amino acids (aa) 280-288), recognized by protective CTL clones, was included in the following peptides: a 9-aa linear peptide (SYVPSAEQI; PyCSP9), a 20-aa linear peptide (aa 280-299; SYVPSAEQILEFVKQISSL; PyCSP20), a MAP containing four branches of PyCSP20 (MAP(280-299)), and a linear peptide and a MAP(MAP(280-299)p2p30) in which PyCSP20 was colinearly synthesized with two universal Th epitopes from tetanus toxin (p2p30). A MAP containing the PyCSP Th epitope (aa 57-70; KIYNRNIVNRLLGD) was included in some experiments. The highest specific lytic activity against peptide-pulsed target cells was obtained with splenocytes from mice immunized with three doses at 3-wk intervals of MAP(280-299)p2p30 in Lipofectin or Lipofectamine. Forty percent of the mice immunized with MAP(280-299)p2p30 and Lipofectin were protected against sporozoite challenge. Immunization with CTL and Th epitopes co-linearly synthesized in a MAP induced significantly better CTL than did immunization with the same sequence as a linear peptide, or immunization with a mixture of two individual MAPs, one with the CTL epitope and the second with the Th epitope.

Publication types

  • Research Support, U.S. Gov't, Non-P.H.S.

MeSH terms

  • Adjuvants, Immunologic / administration & dosage
  • Amino Acid Sequence
  • Animals
  • Antigens, Protozoan / administration & dosage
  • Antigens, Protozoan / genetics
  • Antigens, Protozoan / immunology
  • CD8 Antigens / genetics
  • CD8-Positive T-Lymphocytes / immunology
  • Cytotoxicity, Immunologic* / drug effects
  • Cytotoxicity, Immunologic* / genetics
  • Dose-Response Relationship, Drug
  • Epitopes, T-Lymphocyte / administration & dosage
  • Epitopes, T-Lymphocyte / genetics
  • Epitopes, T-Lymphocyte / immunology
  • Injections, Subcutaneous
  • Liposomes
  • Lymphocyte Activation* / drug effects
  • Lymphocyte Activation* / genetics
  • Malaria / immunology
  • Malaria / parasitology
  • Malaria / prevention & control
  • Mice
  • Mice, Inbred BALB C
  • Molecular Sequence Data
  • Peptide Fragments / administration & dosage
  • Peptide Fragments / immunology*
  • Phosphatidylethanolamines / immunology
  • Plasmodium yoelii / growth & development
  • Plasmodium yoelii / immunology*
  • Protozoan Proteins / immunology*
  • T-Lymphocytes, Cytotoxic / immunology*
  • T-Lymphocytes, Helper-Inducer / chemistry
  • T-Lymphocytes, Helper-Inducer / immunology
  • Tetanus Toxin / immunology
  • Vaccination


  • Adjuvants, Immunologic
  • Antigens, Protozoan
  • CD8 Antigens
  • Epitopes, T-Lymphocyte
  • Liposomes
  • Peptide Fragments
  • Phosphatidylethanolamines
  • Protozoan Proteins
  • Tetanus Toxin
  • circumsporozoite protein, Protozoan
  • 1,2-dielaidoylphosphatidylethanolamine