Naturally Elicited Antibodies to Glycosylphosphatidylinositols (GPIs) of
            <i>Plasmodium falciparum</i>
            Require Intact GPI Structures for Binding and Are Directed Primarily against the Conserved Glycan Moiety

Naik, Ramachandra S.; Gowda, Raghavendra; Ockenhouse, Christian F.; Gowda, D. Channe

doi:10.1128/iai.74.2.1412-1415.2006

Cited by 30 publications

(25 citation statements)

References 16 publications

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“…This finding is not unexpected, since growth-inhibitory activity is a putative measure of antibodies that interfere with merozoite invasion and/or parasite growth and not with other possible components of a protective antibody response, such as (i) blocking the binding of infected RBC (iRBC) to endothelial cells (3,4), (ii) opsonization and destruction of merozoites and iRBC by phagocytic cells (8,21,40), (iii) neutralization of toxic molecules such as glycosylphosphatidylinositol (38,51), and (iv) antibody-dependent cellular inhibition of parasite growth (7).…”

Section: Discussionmentioning

confidence: 89%

In VitroGrowth-Inhibitory Activity and Malaria Risk in a Cohort Study in Mali

et al. 2010

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Immunity to the asexual blood stage of Plasmodium falciparum is complex and likely involves several effector mechanisms. Antibodies are thought to play a critical role in malaria immunity, and a corresponding in vitro correlate of antibody-mediated immunity has long been sought to facilitate malaria vaccine development. The growth inhibition assay (GIA) measures the capacity of antibodies to limit red blood cell (RBC) invasion and/or growth of P. falciparum in vitro. In humans, naturally acquired and vaccine-induced P. falciparum-specific antibodies have growth-inhibitory activity, but it is unclear if growth-inhibitory activity correlates with protection from clinical disease. In a longitudinal study in Mali, purified IgGs, obtained from plasmas collected before the malaria season from 220 individuals aged 2 to 10 and 18 to 25 years, were assayed for growth-inhibitory activity. Malaria episodes were recorded by passive surveillance over the subsequent 6-month malaria season. Logistic regression showed that greater age (odds ratio [OR], 0.78; 95% confidence interval [95% CI], 0.63 to 0.95; P ‫؍‬ 0.02) and growth-inhibitory activity (OR, 0.50; 95% CI, 0.30 to 0.85; P ‫؍‬ 0.01) were significantly associated with decreased malaria risk in children. A growth-inhibitory activity level of 40% was determined to be the optimal cutoff for discriminating malaria-immune and susceptible individuals in this cohort, with a sensitivity of 97.0%, but a low specificity of 24.3%, which limited the assay's ability to accurately predict protective immunity and to serve as an in vitro correlate of antibody-mediated immunity. These data suggest that antibodies which block merozoite invasion of RBC and/or inhibit the intra-RBC growth of the parasite contribute to but are not sufficient for the acquisition of malaria immunity.

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Section: Discussionmentioning

confidence: 89%

In VitroGrowth-Inhibitory Activity and Malaria Risk in a Cohort Study in Mali

et al. 2010

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“…One of the questions in understanding anti‐disease immunity in human malaria is the contribution of anti‐GPI antibodies compared to antibodies against other parasite factors involved in protection against malaria illnesses. People living in endemic areas have anti‐GPI antibodies 8, 20, 24, which might provide some degree of protection against malaria symptoms. High levels of the anti‐GPI antibodies have been correlated with resistance to clinical symptoms, such as anemia and fever 19, and hence these antibodies were suggested to be an important factor in the protective immunity to malaria 8, 11.…”

Section: Discussionmentioning

confidence: 99%

“…P. falciparum GPIs were isolated from the late trophozoite and schizont stages of cultured P. falciparum (FCR3 strain), and purified by HPLC as described earlier 19, 20.…”

Section: Methodsmentioning

confidence: 99%

Inflammatory cytokine and humoral responses to Plasmodium falciparum glycosylphosphatidylinositols correlates with malaria immunity and pathogenesis

Mbengué

Niang

et al. 2015

Immunity, Inflammation and Disease

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Pro‐inflammatory cytokines induced by glycosylphosphatidylinositols (GPIs) of Plasmodium falciparum contribute to malaria pathogenesis and hence, the naturally acquired anti‐GPI antibody thought to provide protection against severe malaria (SM) by neutralizing the stimulatory activity of GPIs. In previous studies, the anti‐GPI antibody levels increased with age in parallel with the development of acquired immunity, and high levels of anti‐GPI antibodies were associated with mild malaria (MM) cases. In the present study, the relationship between the levels of pro‐inflammatory cytokines and anti‐GPI IgG antibody responses, parasitemia, and the clinical outcomes were evaluated in SM and mild malaria (MM) patients. Sera from a total of 110 SM and 72 MM cases after excluding of ineligible patients were analyzed for the levels of anti‐GPI antibodies, IgG subclasses, and cytokine responses by ELISA. While the total anti‐GPI antibody levels were similar in overall SM and MM groups, they were significantly higher in surviving SM patients than in fatal SM cases. In the case of cytokines, the TNF‐α and IL‐6 levels were significantly higher in SM compared to MM, whereas the IL‐10 levels were similar in both groups. The data presented here demonstrate that high levels of the circulatory pro‐inflammatory, TNF‐α, and IL‐6, are indicators of malaria severity, whereas anti‐inflammatory cytokine IL‐10 level does not differentiate SM and MM cases. Further, among SM patients, relatively low levels of anti‐GPI antibodies are indicators of fatal outcomes compared to survivors, suggesting that anti‐GPI antibodies provide some level of protection against SM fatality.

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“…However, the IgGs were shown to kill in vitro by antibody-dependent cell-mediated cytotoxicity (61), suggesting that inducing antibody responses of IgG1 and IgG3 isotypes that interact with activating Fc receptors may be desirable. Antibodies may also confer protection against blood-stage infection by blocking the binding of infected erythrocytes to endothelial cells (62); promoting the opsonization and destruction of merozoites and infected erythrocytes by phagocytic cells (63-65); and neutralizing P. falciparum-derived proinflammatory molecules such as glycosylphosphatidylinositol (GPI) (66,67).…”

Section: Asexual Blood-stage Vaccinesmentioning

confidence: 99%

Advances and challenges in malaria vaccine development

Crompton

Pierce²,

Miller³

2010

J. Clin. Invest.

235

189

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Malaria caused by Plasmodium falciparum remains a major public health threat, especially among children and pregnant women in Africa. An effective malaria vaccine would be a valuable tool to reduce the disease burden and could contribute to elimination of malaria in some regions of the world. Current malaria vaccine candidates are directed against human and mosquito stages of the parasite life cycle, but thus far, relatively few proteins have been studied for potential vaccine development. The most advanced vaccine candidate, RTS,S, conferred partial protection against malaria in phase II clinical trials and is currently being evaluated in a phase III trial in Africa. New vaccine targets need to be identified to improve the chances of developing a highly effective malaria vaccine. A better understanding of the mechanisms of naturally acquired immunity to malaria may lead to insights for vaccine development.

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Naturally Elicited Antibodies to Glycosylphosphatidylinositols (GPIs) of Plasmodium falciparum Require Intact GPI Structures for Binding and Are Directed Primarily against the Conserved Glycan Moiety

Cited by 30 publications

References 16 publications

In VitroGrowth-Inhibitory Activity and Malaria Risk in a Cohort Study in Mali

In VitroGrowth-Inhibitory Activity and Malaria Risk in a Cohort Study in Mali

Inflammatory cytokine and humoral responses to Plasmodium falciparum glycosylphosphatidylinositols correlates with malaria immunity and pathogenesis

Advances and challenges in malaria vaccine development

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