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Memórias do Instituto Oswaldo Cruz

versión impresa ISSN 0074-0276versión On-line ISSN 1678-8060

Mem. Inst. Oswaldo Cruz v.87  supl.3 Rio de Janeiro  1992 

T cell responses to repeat and non-repeat regions of the circumsporozoite protein detected in volunteers immunized with Plasmodium falciparum sporozoites

Elizabeth Nardin1 

Yamuna Dona Munesinghe2 

Alberto Moreno1 

Pedro Clavijo1 

Mauricio Calvo Calle1 

Robert Edelman3 

Jonathan Davis3 

Deirdre Herrington4 

Ruth S. Nussenzweig1 

New York University Medical Center, Department of Medical and Molecular Parasitology, New York, USA

University of Colombo, Department of Zoology, Colombo, Sri Lanka

University of Maryland, Center for Vaccine Development, Baltimore, USA

Wake-Forest Univesity, Bowman-Gray School of Medicine, Division of Infectious Diseases, Winston-Salem, USA


The design of malarial vaccine based on the circumsporozoite (CS) protein, a majuor 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 wich 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 C57B1 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 volunteers, and the recent studies inthe rodent model (Renia et al., 1991; Tsuji et al., 1990), suggested 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.

Key words: malaria sporozoites; CS protein; human CD4+ T cells; epitopes; vaccines


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