Association between Naturally Acquired Antibodies to Erythrocyte‐Binding Antigens of<i>Plasmodium falciparum</i>and Protection from Malaria and High‐Density Parasitemia

Richards, Jack S.; Stanisic, Danielle I.; Fowkes, Freya J. I.; Tavul, Livingstone; Dabod, Elijah; Thompson, J. K.; Kumar, Sanjeev; Chitnis, Chetan E.; Narum, David L.; Michon, P; Siba, Peter; Cowman, Alan F.; Müeller, Ivo; Beeson, James G.

doi:10.1086/656413

Cited by 186 publications

(222 citation statements)

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“…Although some children had multiple episodes of parasitemia or symptomatic malaria, the analysis presented examined the time to first symptomatic episode only. This is consistent with previous analytic approaches used in this cohort (48)(49)(50)(51). A range of demographic, clinical, and biological variables was assessed as potential confounders of associations between Abs and malaria outcomes.…”

Section: Discussionsupporting

confidence: 61%

“…All statistical analyses were performed using STATA 9.2 (StataCorp) or Prism 5.01 (GraphPad) software. Ab responses to MSP1-19, MSP2, AMA1, EBAs, PfRh2, and PfRh4 in this population were reported previously (48)(49)(50)(51), and the data were reanalyzed for comparison with other Ags and in combination analyses.…”

Section: Discussionmentioning

confidence: 98%

“…Therefore, all Cox-regression analyses were performed unadjusted and with adjustments for these previously defined covariates in this study cohort (22,50). Previous analyses in this cohort showed that concurrent parasitemia and erythrocyte polymorphisms are not significant confounders (48,52). Regression analysis investigating multiple Ab responses was limited by their highly correlated nature.…”

Section: Discussionmentioning

confidence: 99%

“…It is likely that protective immunity targeting merozoites consists of a repertoire of responses targeting multiple Ags and that a multivalent vaccine will be required to induce an efficacious response. However, very few studies examined this issue in human populations, and only a small number of merozoite Ag combinations has been studied (16,17,48).…”

Section: Discussionmentioning

confidence: 99%

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Identification and Prioritization of Merozoite Antigens as Targets of Protective Human Immunity to Plasmodium falciparum Malaria for Vaccine and Biomarker Development

Richards

Arumugam

Reiling

et al. 2013

The Journal of Immunology

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231

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The development of effective malaria vaccines and immune biomarkers of malaria is a high priority for malaria control and elimination. Ags expressed by merozoites of Plasmodium falciparum are likely to be important targets of human immunity and are promising vaccine candidates, but very few Ags have been studied. We developed an approach to assess Ab responses to a comprehensive repertoire of merozoite proteins and investigate whether they are targets of protective Abs. We expressed 91 recombinant proteins, located on the merozoite surface or within invasion organelles, and screened them for quality and reactivity to human Abs. Subsequently, Abs to 46 proteins were studied in a longitudinal cohort of 206 Papua New Guinean children to define Ab acquisition and associations with protective immunity. Ab responses were higher among older children and those with active parasitemia. High-level Ab responses to rhoptry and microneme proteins that function in erythrocyte invasion were identified as being most strongly associated with protective immunity compared with other Ags. Additionally, Abs to new or understudied Ags were more strongly associated with protection than were Abs to current vaccine candidates that have progressed to phase 1 or 2 vaccine trials. Combinations of Ab responses were identified that were more strongly associated with protective immunity than responses to their single-Ag components. This study identifies Ags that are likely to be key targets of protective human immunity and facilitates the prioritization of Ags for further evaluation as vaccine candidates and/or for use as biomarkers of immunity in malaria surveillance and control.

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Section: Discussionsupporting

confidence: 61%

Section: Discussionmentioning

confidence: 98%

Section: Discussionmentioning

confidence: 99%

Section: Discussionmentioning

confidence: 99%

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Identification and Prioritization of Merozoite Antigens as Targets of Protective Human Immunity to Plasmodium falciparum Malaria for Vaccine and Biomarker Development

Richards

Arumugam

Reiling

et al. 2013

The Journal of Immunology

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209

231

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“…High-titre antibodies against EBA-175 RII are associated with protection from clinical malaria in children (Okenu et al, 2000;McCarra et al, 2011), although such association is not clear in some studies or has not been observed in groups having low incidence of disease (Osier et al, 2008;Richards et al, 2010) It has been suggested that EBA-175 RII polymorphism has shown immune selection aimed at maintaining genetic diversity in parasite populations. This polymorphism may contribute towards the lack of association with protective immunity in some cohort studies, depending on which strain the antigen used in these studies originated from, and would affect the ability of antibodies specific for EBA-175 to block invasion (Baum et al, 2003;Jiang et al, 2011;Healer et al, 2013).…”

Section: Antibody Reactivity From Individuals Living In Endemic Areasmentioning

confidence: 99%

Far from the Madding Crowd: the Molecular Basis for Immunological Escape ofPlasmodium falciparum

Patarroyo¹,

Aza-Conde²,

Moreno-Vranich³

et al. 2017

Current Issues in Molecular Biology

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Like Thomas Hardy's famous novel Far from the Madding Crowd, Plasmodium falciparum parasites display their most relevant survival structures (proteins) involved in host cell invasion far away from the immune system's susceptible regions, displaying tremendous genetic variability, to attract the immune response and escape immune pressure. The 3D structure localisation of the conserved amino acid sequences of this deadly parasite's most relevant proteins involved in host cell invasion, as well as the location of the highly polymorphic, h i g h l y i m m u n o g e n i c r e g i o n s , c l e a r l y demonstrates that such structures are far apart, sometimes 90° to 180° opposite, thereby rendering the immune response useless. It is also shown here that these conserved, f u n c t i o n a l l y -r e l e v a n t s t r u c t u r e s a r e immunologically silent, since no immune response has been induced.

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Complement in malaria: immune evasion strategies and role in protective immunity

2020

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The malaria parasite has for long been thought to escape host complement attack as a survival strategy. However, it was only recently that complement evasion mechanisms of the parasite were described. Simultaneously, the role of complement in antibody‐mediated naturally acquired and vaccine‐induced protection against malaria has also been reported. Such findings should be considered in future vaccine design, given the current need to develop more efficacious vaccines against malaria. Parasite antigens derived from molecules mediating functions crucial for parasite survival, such as complement evasion, or parasite antigens against which antibody responses lead to an efficient complement attack could present new candidates for vaccines. In this review, we discuss recent findings on complement evasion by the malaria parasites and the emerging role of complement in antibody‐mediated protection against malaria. We emphasize that immune responses to vaccines based on complement inhibitors should not only induce complement‐activating antibodies but also neutralize the escape mechanisms of the parasite.

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Association between Naturally Acquired Antibodies to Erythrocyte‐Binding Antigens ofPlasmodium falciparumand Protection from Malaria and High‐Density Parasitemia

Abstract: The EBAs appear important targets of acquired protective immunity. These findings support their further development as vaccine candidates.

Cited by 186 publications

References 40 publications

Identification and Prioritization of Merozoite Antigens as Targets of Protective Human Immunity to Plasmodium falciparum Malaria for Vaccine and Biomarker Development

Identification and Prioritization of Merozoite Antigens as Targets of Protective Human Immunity to Plasmodium falciparum Malaria for Vaccine and Biomarker Development

Far from the Madding Crowd: the Molecular Basis for Immunological Escape ofPlasmodium falciparum

Complement in malaria: immune evasion strategies and role in protective immunity

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