Antibody targets on the surface of plasmodium falciparum- infected erythrocytes that are associated with immunity to severe malaria in young children

Jo Anne Chan, Michelle J. Boyle, Kerryn A. Moore, Linda Reiling, Zaw Lin, Wina Hasang, Marion Avril, Laurens Manning, Ivo Mueller, Moses Laman, Timothy Davis, Joseph D. Smith, Stephen J. Rogerson, Julie A. Simpson, Freya J.I. Fowkes, James G. Beeson

Research output: Contribution to journalArticle

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Abstract

Background Sequestration of Plasmodium falciparum-infected erythrocytes (IEs) in the microvasculature contributes to pathogenesis of severe malaria in children. This mechanism is mediated by antigens expressed on the IE surface. However, knowledge of specific targets and functions of antibodies to IE surface antigens that protect against severe malaria is limited. Methods Antibodies to IE surface antigens were examined in a case-control study of young children in Papua New Guinea presenting with severe or uncomplicated malaria (n = 448), using isolates with a virulent phenotype associated with severe malaria, and functional opsonic phagocytosis assays. We used genetically modified isolates and recombinant P. falciparum erythrocyte membrane protein 1 (PfEMP1) domains to quantify PfEMP1 as a target of antibodies associated with disease severity. Results Antibodies to the IE surface and recombinant PfEMP1 domains were significantly higher in uncomplicated vs severe malaria and were boosted following infection. The use of genetically modified P. falciparum revealed that PfEMP1 was a major target of antibodies and that PfEMP1-specific antibodies were associated with reduced odds of severe malaria. Furthermore, antibodies promoting the opsonic phagocytosis of IEs by monocytes were lower in those with severe malaria. Conclusions Findings suggest that PfEMP1 is a dominant target of antibodies associated with reduced risk of severe malaria, and function in part by promoting opsonic phagocytosis.

Original languageEnglish
Pages (from-to)819-828
Number of pages10
JournalJournal of Infectious Diseases
Volume219
Issue number5
DOIs
Publication statusPublished - 15 Feb 2019

Fingerprint

Plasmodium falciparum
Malaria
Immunity
Erythrocytes
Antibodies
Phagocytosis
Erythrocyte Membrane
Surface Antigens
Membrane Proteins
Papua New Guinea
Microvessels
Case-Control Studies
Monocytes
Phenotype
Antigens
Plasmodium falciparum erythrocyte membrane protein 1
Infection

Cite this

Chan, Jo Anne ; Boyle, Michelle J. ; Moore, Kerryn A. ; Reiling, Linda ; Lin, Zaw ; Hasang, Wina ; Avril, Marion ; Manning, Laurens ; Mueller, Ivo ; Laman, Moses ; Davis, Timothy ; Smith, Joseph D. ; Rogerson, Stephen J. ; Simpson, Julie A. ; Fowkes, Freya J.I. ; Beeson, James G. / Antibody targets on the surface of plasmodium falciparum- infected erythrocytes that are associated with immunity to severe malaria in young children. In: Journal of Infectious Diseases. 2019 ; Vol. 219, No. 5. pp. 819-828.
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title = "Antibody targets on the surface of plasmodium falciparum- infected erythrocytes that are associated with immunity to severe malaria in young children",
abstract = "Background Sequestration of Plasmodium falciparum-infected erythrocytes (IEs) in the microvasculature contributes to pathogenesis of severe malaria in children. This mechanism is mediated by antigens expressed on the IE surface. However, knowledge of specific targets and functions of antibodies to IE surface antigens that protect against severe malaria is limited. Methods Antibodies to IE surface antigens were examined in a case-control study of young children in Papua New Guinea presenting with severe or uncomplicated malaria (n = 448), using isolates with a virulent phenotype associated with severe malaria, and functional opsonic phagocytosis assays. We used genetically modified isolates and recombinant P. falciparum erythrocyte membrane protein 1 (PfEMP1) domains to quantify PfEMP1 as a target of antibodies associated with disease severity. Results Antibodies to the IE surface and recombinant PfEMP1 domains were significantly higher in uncomplicated vs severe malaria and were boosted following infection. The use of genetically modified P. falciparum revealed that PfEMP1 was a major target of antibodies and that PfEMP1-specific antibodies were associated with reduced odds of severe malaria. Furthermore, antibodies promoting the opsonic phagocytosis of IEs by monocytes were lower in those with severe malaria. Conclusions Findings suggest that PfEMP1 is a dominant target of antibodies associated with reduced risk of severe malaria, and function in part by promoting opsonic phagocytosis.",
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author = "Chan, {Jo Anne} and Boyle, {Michelle J.} and Moore, {Kerryn A.} and Linda Reiling and Zaw Lin and Wina Hasang and Marion Avril and Laurens Manning and Ivo Mueller and Moses Laman and Timothy Davis and Smith, {Joseph D.} and Rogerson, {Stephen J.} and Simpson, {Julie A.} and Fowkes, {Freya J.I.} and Beeson, {James G.}",
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Chan, JA, Boyle, MJ, Moore, KA, Reiling, L, Lin, Z, Hasang, W, Avril, M, Manning, L, Mueller, I, Laman, M, Davis, T, Smith, JD, Rogerson, SJ, Simpson, JA, Fowkes, FJI & Beeson, JG 2019, 'Antibody targets on the surface of plasmodium falciparum- infected erythrocytes that are associated with immunity to severe malaria in young children' Journal of Infectious Diseases, vol. 219, no. 5, pp. 819-828. https://doi.org/10.1093/infdis/jiy580

Antibody targets on the surface of plasmodium falciparum- infected erythrocytes that are associated with immunity to severe malaria in young children. / Chan, Jo Anne; Boyle, Michelle J.; Moore, Kerryn A.; Reiling, Linda; Lin, Zaw; Hasang, Wina; Avril, Marion; Manning, Laurens; Mueller, Ivo; Laman, Moses; Davis, Timothy; Smith, Joseph D.; Rogerson, Stephen J.; Simpson, Julie A.; Fowkes, Freya J.I.; Beeson, James G.

In: Journal of Infectious Diseases, Vol. 219, No. 5, 15.02.2019, p. 819-828.

Research output: Contribution to journalArticle

TY - JOUR

T1 - Antibody targets on the surface of plasmodium falciparum- infected erythrocytes that are associated with immunity to severe malaria in young children

AU - Chan, Jo Anne

AU - Boyle, Michelle J.

AU - Moore, Kerryn A.

AU - Reiling, Linda

AU - Lin, Zaw

AU - Hasang, Wina

AU - Avril, Marion

AU - Manning, Laurens

AU - Mueller, Ivo

AU - Laman, Moses

AU - Davis, Timothy

AU - Smith, Joseph D.

AU - Rogerson, Stephen J.

AU - Simpson, Julie A.

AU - Fowkes, Freya J.I.

AU - Beeson, James G.

PY - 2019/2/15

Y1 - 2019/2/15

N2 - Background Sequestration of Plasmodium falciparum-infected erythrocytes (IEs) in the microvasculature contributes to pathogenesis of severe malaria in children. This mechanism is mediated by antigens expressed on the IE surface. However, knowledge of specific targets and functions of antibodies to IE surface antigens that protect against severe malaria is limited. Methods Antibodies to IE surface antigens were examined in a case-control study of young children in Papua New Guinea presenting with severe or uncomplicated malaria (n = 448), using isolates with a virulent phenotype associated with severe malaria, and functional opsonic phagocytosis assays. We used genetically modified isolates and recombinant P. falciparum erythrocyte membrane protein 1 (PfEMP1) domains to quantify PfEMP1 as a target of antibodies associated with disease severity. Results Antibodies to the IE surface and recombinant PfEMP1 domains were significantly higher in uncomplicated vs severe malaria and were boosted following infection. The use of genetically modified P. falciparum revealed that PfEMP1 was a major target of antibodies and that PfEMP1-specific antibodies were associated with reduced odds of severe malaria. Furthermore, antibodies promoting the opsonic phagocytosis of IEs by monocytes were lower in those with severe malaria. Conclusions Findings suggest that PfEMP1 is a dominant target of antibodies associated with reduced risk of severe malaria, and function in part by promoting opsonic phagocytosis.

AB - Background Sequestration of Plasmodium falciparum-infected erythrocytes (IEs) in the microvasculature contributes to pathogenesis of severe malaria in children. This mechanism is mediated by antigens expressed on the IE surface. However, knowledge of specific targets and functions of antibodies to IE surface antigens that protect against severe malaria is limited. Methods Antibodies to IE surface antigens were examined in a case-control study of young children in Papua New Guinea presenting with severe or uncomplicated malaria (n = 448), using isolates with a virulent phenotype associated with severe malaria, and functional opsonic phagocytosis assays. We used genetically modified isolates and recombinant P. falciparum erythrocyte membrane protein 1 (PfEMP1) domains to quantify PfEMP1 as a target of antibodies associated with disease severity. Results Antibodies to the IE surface and recombinant PfEMP1 domains were significantly higher in uncomplicated vs severe malaria and were boosted following infection. The use of genetically modified P. falciparum revealed that PfEMP1 was a major target of antibodies and that PfEMP1-specific antibodies were associated with reduced odds of severe malaria. Furthermore, antibodies promoting the opsonic phagocytosis of IEs by monocytes were lower in those with severe malaria. Conclusions Findings suggest that PfEMP1 is a dominant target of antibodies associated with reduced risk of severe malaria, and function in part by promoting opsonic phagocytosis.

KW - antibodies

KW - immunity

KW - PfEMP1

KW - Plasmodium falciparum

KW - severe malaria

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