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There is longstanding evidence that immunoglobulin G (IgG) has a role in protection against clinical malaria, and human antibodies of the cytophilic subclasses are thought to be particularly critical in this respect. In this cohort study, 286 Burkinabè children 6 months to 15 years old were kept under malaria surveillance in order to assess the protective role of antibody responses against four antigens which are currently being evaluated as vaccine candidates: apical membrane antigen 1 (AMA1), merozoite surface protein 1-19 (MSP1-19), MSP3, and glutamate-rich protein (GLURP). Total IgG, IgM, and IgG subclass responses were measured just before the malaria transmission season. The incidence of malaria was 2.4 episodes per child year of risk. After adjusting for the confounding effects of age, the level of total IgG to GLURP was strongly associated with reduced malaria incidence (incidence rate ratio associated with a doubling of total IgG, 0.79; 95% confidence interval, 0.66 to 0.94; P ‫؍‬ 0.009.); there was a borderline statistically significant association between the level of total IgG to MSP3 and malaria incidence and no evidence of an association for total IgG to AMA1 and to MSP1-19. Of the IgG subclass responses studied, only IgG3 and IgG4 against GLURP and IgG1 against AMA1 were associated with reduced risk of clinical malaria. There was no evidence of an interaction between responses to AMA1 and baseline parasitemia in their effects on malaria incidence. Currently included in malaria vaccine formulations for clinical trials in humans, these blood-stage antigens, AMA1 and GLURP, offer good prospects for malaria vaccine development.In sub-Saharan Africa, the clinical manifestations of malaria are caused by asexual blood stages of Plasmodium falciparum, and antigens on asexual parasite stages in the bloodstream are critical in the development of protective immunity to the disease. After repeated exposure, nonsterile immunity to malaria can be acquired by people living in areas of endemicity. Strong evidence exists, from the passive transfer of antibodies between immune and nonimmune individuals, that this immunity can be antibody mediated (18,29,40). The most efficient in vivo model for this antibody-mediated parasite control in areas where the disease is endemic requires the participation of monocytes and has been called antibody-dependent cellular inhibition (ADCI) (24,26). This assay is assumed to mimic the in vivo cooperation between monocytes and cytophilic parasite-specific antibodies and is considered a surrogate marker of immunity against P. falciparum blood stages (21). BouharounTayoun and Druilhe observed profound differences in the distribution of immunoglobulin (Ig) subclasses between clinically protected and susceptible individuals, with cytophilic subclasses (immunoglobulin G1 [IgG1] and IgG3) being dominant in protected individuals (10). In different epidemiological settings, similar findings have been made, underscoring the importance of cytophilic antibodies against blood-stage antigens in ...

Background: Antigen-specific antibody-mediated immune responses play an important role in natural protection against clinical malaria, but conflicting estimates of this association have emerged from immuno-epidemiological studies in different geographical settings. This study was aimed at assessing in a standardized manner the relationship between the antibody responses to four malaria vaccine candidate antigens and protection from clinical malaria, in a cohort of Ghanaian children.

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The recombinant human (rh) myelin/oligodendrocyte glycoprotein (MOG)-induced experimental autoimmune encephalomyelitis (EAE) model in the common marmoset is characterized by 100% disease incidence, a chronic disease course, and a variable time interval between immunization and neurological impairment. We investigated whether monkeys with fast and slow disease progression display different anti-MOG T or B cell responses and analyzed the underlying pathogenic mechanism(s). The results show that fast progressor monkeys display a significantly wider specificity diversification of anti-MOG T cells at necropsy than slow progressors, especially against MOG34–56 and MOG74–96. MOG34–56 emerged as a critical encephalitogenic peptide, inducing severe neurological disease and multiple lesions with inflammation, demyelination, and axonal injury in the CNS. Although EAE was not observed in MOG74–96-immunized monkeys, weak T cell responses against MOG34–56 and low grade CNS pathology were detected. When these cases received a booster immunization with MOG34–56 in IFA, full-blown EAE developed. MOG34–56-reactive T cells expressed CD3, CD4, or CD8 and CD56, but not CD16. Moreover, MOG34–56-specific T cell lines displayed specific cytotoxic activity against peptide-pulsed B cell lines. The phenotype and cytotoxic activity suggest that these cells are NK-CTL. These results support the concept that cytotoxic cells may play a role in the pathogenesis of multiple sclerosis.