T cell responses to repeat and non-repeat regions of the circumsporozoite protein detected in volunteers immunized with Plasmodium falciparum sporozoites.
The design of a malarial vaccine based on the circumsporozoite (CS) protein, a major surface antigen of the sporozoite stage of the malaria parasite, requires the identification of T and B cell epitopes for inclusion in recombinant or synthetic vaccine candidates. We have investigated the specificity and function of a series of T cell clones, derived from volunteers immunized with Plasmodium falciparum sporozoites, in an effort to identify relevant epitopes in the immune response to the pre-erythrocytic stages of the parasite. CD4+ T cell clones were obtained which specifically recognized a repetitive epitope located in the 5' repeat region of the CS protein. This epitope, when conjugated to the 3' repeat region in a synthetic MAPs construct, induced high titers of antisporozoite antibodies in C57BL mice. A second T cell epitope, which mapped to aa 326-345 of the carboxy terminal, was recognized by lytic, as well as non-lytic, CD4+ T cells derived from the sporozoite-immunized volunteers. The demonstration of CD4+ CTL in the human volunteers, and the recent studies in the rodent model (Renia et al., 1991; Tsuji et al., 1990), suggest that CS-specific CD4+ T cells, in addition to their indirect role as helper cells in the induction of antibody and CD8+ effector cells, may also play a direct role in protection against sporozoite challenge by targeting EEF within the liver.
Department of Medical and Molecular Parasitology, New York University Medical Center, NY 10010.
E
E
Nardin
Y D
YD
Munesinghe
A
A
Moreno
P
P
Clavijo
M C
MC
Calle
R
R
Edelman
J
J
Davis
D
D
Herrington
R S
RS
Nussenzweig
D000595:Amino Acid Sequence; D000818:Animals; D000953:Antigens, Protozoan / Q000235:genetics / Q000276:immunology*; D015496:CD4-Positive T-Lymphocytes / Q000276:immunology; D002999:Clone Cells / Q000276:immunology; D016056:Immunodominant Epitopes / Q000276:immunology; D017780:Malaria Vaccines / Q000276:immunology*; D016778:Malaria, Falciparum / Q000276:immunology / Q000517:prevention & control; D051379:Mice; D008810:Mice, Inbred C57BL; D008969:Molecular Sequence Data; D010963:Plasmodium falciparum / Q000235:genetics / Q000276:immunology*; D015800:Protozoan Proteins / Q000235:genetics / Q000276:immunology*; D012091:Repetitive Sequences, Nucleic Acid; D013601:T-Lymphocytes / Q000276:immunology*; D014611:Vaccination
D000953:Antigens, Protozoan; D016056:Immunodominant Epitopes; D017780:Malaria Vaccines; D015800:Protozoan Proteins; C041595:circumsporozoite protein, Protozoan