Immunity to malarial infections in human populations is known to affect the development of the asexual blood stages of the parasites in the human host and to be capable of conferring significant protection against morbidity and mortality due to the disease. In this study we show that during acute infection with Plasmodium vivax malaria, one of the two main malarial pathogens of humans, most individuals also develop immunity that suppresses the infectivity of the sexual stages of the parasite to mosquitoes. The immunity is antibody mediated and is directed against the parasites in the mosquito midgut shortly after ingestion of blood by a mosquito. This immunity could be expected to have significant effects on the natural transmission of P. vivax malaria.
Antibodies were raised in rabbits by immunizing against fresh unfixed or cryopreserved female gametes of the human malaria pathogen Plasmodium vivax. The antibodies were shown to react with the surface of gametes by the indirect immunofluorescent test. When parasite isolates from P. vivax infected individuals were fed through a membrane to Anopheles tessellatus mosquitoes in the presence of immune rabbit sera, they completely blocked the infectivity of the parasite isolates to the vector. Immunoglobulins separated from these sera also blocked infectivity to the same extent as did the immune sera indicating that antibodies were responsible for the transmission blocking effect of the sera. This study indicated that P. vivax like other malaria parasites is highly susceptible to anti gamete transmission blocking immunity.
The infectivity to mosquitoes of 31 acute Plasmodium vivax patients was measured by permitting mosquitoes to feed directly on the patients. The infectivity of these patients correlated closely with titers of antibodies in their serum as measured by indirect immunofluorescence against air-dried female gametes of P. vivax. Infectivity by direct feeding was also closely parallel to the transmission-blocking activity of the sera of patients as measured by the suppression of infectivity of parasitized blood by autologous serum relative to normal (nonmalarial) human serum when fed to mosquitoes through a membrane. These results are consistent with serum antibodies in human P. vivax infections as major factors determining the infectivity of an infected individual to mosquitoes. It was further noted that individuals having a second attack of P. vivax within less than 4 months were considerably less infectious to mosquitoes than first-attack patients were. This "boosting" of transmission-blocking immunity was much less if longer intervals intervened between attacks. We discuss the immunological implications and possible epidemiological significance of this short-term boosting of transmission-blocking immunity by successive P. vivax infections.
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.
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