Antibodies to variable Plasmodium falciparum-infected erythrocyte surface antigens are associated with protection from novel malaria infections

Giha, Hayder A.; Staalsøe, Trine; Dodoo, Daniel; Roper, Cally; Satti, Gwiria M. H.; Arnot, David E.; Hviid, Lars; Theander, Thor G.

doi:10.1016/s0165-2478(99)00173-x

Cited by 114 publications

(101 citation statements)

References 27 publications

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“…c Percentage of individuals in the 1342 cohort with a measurable IgG response to the domain. mediators of immunity acquired by individuals living in malaria endemic areas (33)(34)(35)(36). Furthermore, parasites from individuals with a narrow repertoire of anti-VSA Abs tend to express VSA types to which children in endemic areas develop Abs early in life, whereas parasites infecting individuals with a broad anti-VSA IgG repertoire express VSA types to which Abs develop later in life (18,37).…”

Section: Discussionmentioning

confidence: 99%

Sequential, Ordered Acquisition of Antibodies to Plasmodium falciparum Erythrocyte Membrane Protein 1 Domains

Cham

Turner

Lusingu

et al. 2009

The Journal of Immunology

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128

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Section: Discussionmentioning

confidence: 99%

Sequential, Ordered Acquisition of Antibodies to Plasmodium falciparum Erythrocyte Membrane Protein 1 Domains

Cham

Turner

Lusingu

et al. 2009

The Journal of Immunology

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113

128

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“…20). Although this acquisition of protective immunity is paralleled by acquisition of both cell-mediated and humoral immune responses to a long list of parasite Ags, a growing body of evidence points to an important role of Abs specific for parasite-encoded VSA expressed on the surface of infected erythrocytes (5,(21)(22)(23). The best-characterized VSA is P. falciparum erythrocyte membrane protein 1 (PfEMP1), which is encoded by the var gene family containing 40 -50 members/genome.…”

Section: Discussionmentioning

confidence: 99%

Plasmodium falciparum Variant Surface Antigen Expression Varies Between Isolates Causing Severe and Nonsevere Malaria and Is Modified by Acquired Immunity

Nielsen

Staalsøe

Kurtzhals

et al. 2002

The Journal of Immunology

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187

221

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In areas of endemic parasite transmission, protective immunity to Plasmodium falciparum malaria is acquired over several years with numerous disease episodes. Acquisition of Abs to parasite-encoded variant surface Ags (VSA) on the infected erythrocyte membrane is important in the development of immunity, as disease-causing parasites appear to be those not controlled by preexisting VSA-specific Abs. In this work we report that VSA expressed by parasites from young Ghanaian children with P. falciparum malaria were commonly and strongly recognized by plasma Abs from healthy children in the same area, whereas recognition of VSA expressed by parasites from older children was weaker and less frequent. Independent of this, parasites isolated from children with severe malaria (cerebral malaria and severe anemia) were better recognized by VSA-specific plasma Abs than parasites obtained from children with nonsevere disease. This was not due to a higher infection multiplicity in younger patients or in patients with severe disease. Our data suggest that acquisition of VSA-specific Ab responses gradually restricts the VSA repertoire that is compatible with parasite survival in the semi-immune host. This appears to limit the risk of severe disease by discriminating against the expression of VSA likely to cause life-threatening complications, such as cerebral malaria and severe anemia. Such VSA seem to be preferred by parasites infecting a nonimmune host, suggesting that VSA expression and switching are not random, and that the VSA expression pattern is modulated by immunity. This opens the possibility of developing morbidity-reducing vaccines targeting a limited subset of common and particularly virulent VSA.

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“…As others have convincingly shown, such "gaps" in recognition are associated with malaria episodes in individuals with low immunity and also with P. falciparum infections in pregnant women. 4,32,33,48,49 The level of anti-VSA antibodies, furthermore, has been shown to correlate with adhesion inhibition, itself a surrogate marker of protection against P. falciparum infection. 49,50 Thus, we believe the data presented here provide further evidence for an immunologic basis to the explanation of the radically different susceptibility to malaria in the two groups of children in our study.…”

Section: Discussionmentioning

confidence: 99%

“…16,[23][24][25] Numerous studies have demonstrated the wide diversity of VSA. 5,6,20,[26][27][28][29][30][31][32][33] Nevertheless, VSA do contain regions that are either identical or antigenically cross-reactive, and conserved epitopes are present in PfEMP-1. 34,35 More-recent studies have confirmed that VSA contain cross-reactive epitopes, lending support to the idea that these molecules could be used in the design of antiadhesive therapeutics.…”

Section: Introductionmentioning

confidence: 99%

Low antibody responses to variant surface antigens of Plasmodium falciparum are associated with severe malaria and increased susceptibility to malaria attacks in Gabonese children.

Tebo

Kremsner²,

Piper³

et al. 2002

Am J Trop Med Hyg

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Abstract:We measured the levels of IgG antibodies with specificity for the variant surface antigens (VSA) of Plasmodium falciparum in plasma samples from a cohort of Gabonese children participating in a longitudinal casecontrol malaria study. Children with mild malaria had significantly higher anti-VSA IgG responses than their matched counterparts with severe malaria, most markedly during convalescence and when they were healthy. Over the course of the study, almost twice as many children who presented initially with mild rather than severe malaria developed antibodies recognizing the VSA expressed by each of a panel of three isolates, and those with the highest anti-VSA IgG responses had the lowest malaria attack rates. The results suggest that the clinical outcome of P. falciparum infection in young African children depends on their ability to both develop and maintain a broad profile of anti-VSA IgG antibodies, and that this ability is diminished in children who have experienced a severe malaria attack.

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Antibodies to variable Plasmodium falciparum-infected erythrocyte surface antigens are associated with protection from novel malaria infections

Cited by 114 publications

References 27 publications

Sequential, Ordered Acquisition of Antibodies to Plasmodium falciparum Erythrocyte Membrane Protein 1 Domains

Sequential, Ordered Acquisition of Antibodies to Plasmodium falciparum Erythrocyte Membrane Protein 1 Domains

Plasmodium falciparum Variant Surface Antigen Expression Varies Between Isolates Causing Severe and Nonsevere Malaria and Is Modified by Acquired Immunity

Low antibody responses to variant surface antigens of Plasmodium falciparum are associated with severe malaria and increased susceptibility to malaria attacks in Gabonese children.

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