Elicitation of specific cytotoxic T cells by immunization with malaria soluble synthetic polypeptides.
We have studied the immunogenicity of Plasmodium falciparum circumsporozoite (CS) protein-derived synthetic polypeptides in mice. These synthetic peptides correspond to the N- and the C-terminal domains 22-125 and 289-390, respectively of the P. falciparum 7G8 isolate CS protein expressed on the sporozoite surface. They comprise what is believed to be the mature protein, except for the central repetitive B cell domain. BALB/c (H-2d) mice were immunized s.c. with 50 micrograms soluble CS polypeptides emulsified in IFA. After a single immunization, CS-specific helper and cytotoxic T lymphocytes (CTLs) could be obtained. The resultant CTLs obtained by in vitro restimulation of primed lymph node (LN) cells recognized H-2Kd target cells in the presence of short synthetic peptides defined in the present study. These epitopes are contained within the N- and C-terminal regions of the CS protein, and correspond to sequences 39-47 and 333-342. In addition, these CTLs can specifically lyse H-2d target cells transfected with the CS gene. These results suggest that, by immunization of mice with large soluble CS synthetic polypeptides in IFA, it is possible to obtain MHC class I-restricted T cell responses specific for the CS protein. This approach might be advantageous in the formulation of efficient malaria subunit vaccines.
Blum-Tirouvanziam
U
U
Institute of Biochemistry, University of Lausanne, Epalinges, Switzerland.
Beghdadi-Rais
C
C
Roggero
M A
MA
Valmori
D
D
Bertholet
S
S
Bron
C
C
Fasel
N
N
Corradin
G
G
D000595:Amino Acid Sequence; D000818:Animals; D006183:H-2 Antigens / Q000276:immunology; D017780:Malaria Vaccines / Q000276:immunology*; D051379:Mice; D008807:Mice, Inbred BALB C; D008969:Molecular Sequence Data; D010446:Peptide Fragments / Q000096:biosynthesis / Q000276:immunology*; D015800:Protozoan Proteins / Q000096:biosynthesis / Q000276:immunology*; D011994:Recombinant Proteins / Q000096:biosynthesis; D013602:T-Lymphocytes, Cytotoxic / Q000276:immunology*; D014162:Transfection
D006183:H-2 Antigens; D017780:Malaria Vaccines; D010446:Peptide Fragments; D015800:Protozoan Proteins; D011994:Recombinant Proteins; C041595:circumsporozoite protein, Protozoan