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Memórias do Instituto Oswaldo Cruz

versión impresa ISSN 0074-0276

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

http://dx.doi.org/10.1590/S0074-02761992000700037 

T cell responses to repeat and non-repeat regions of the circumsporozoite protein detected in volunteers immunized with Plasmodium falciparum sporozoitesNardinElizabethMunesingheYamuna DonaMorenoAlbertoClavijoPedroCalleMauricio CalvoEdelmanRobertDavisJonathanHerringtonDeirdreNussenzweigRuth S. 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 001992873223227The 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.malaria sporozoitesCS proteinhuman CD4+ T cellsepitopesvaccinesFull text available only in PDF format.Texto completo disponível apenas em PDF.