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Afucosylated Plasmodium falciparum-specific IgG is induced by infection but not by subunit vaccination

Author

Listed:
  • Mads Delbo Larsen

    (Sanquin Research
    University of Amsterdam)

  • Mary Lopez-Perez

    (University of Copenhagen)

  • Emmanuel Kakra Dickson

    (University of Ghana)

  • Paulina Ampomah

    (University of Cape Coast)

  • Nicaise Tuikue Ndam

    (Université de Paris, MERIT, IRD)

  • Jan Nouta

    (Leiden University Medical Center)

  • Carolien A. M. Koeleman

    (Leiden University Medical Center)

  • Agnes L. Hipgrave Ederveen

    (Leiden University Medical Center)

  • Benjamin Mordmüller

    (Radboud University Medical Center
    Universitätsklinikum Tübingen)

  • Ali Salanti

    (University of Copenhagen)

  • Morten Agertoug Nielsen

    (University of Copenhagen)

  • Achille Massougbodji

    (Université d’Abomey-Calavi)

  • C. Ellen Schoot

    (Sanquin Research
    University of Amsterdam)

  • Michael F. Ofori

    (University of Ghana)

  • Manfred Wuhrer

    (Leiden University Medical Center)

  • Lars Hviid

    (University of Copenhagen
    Department of Infectious Diseases)

  • Gestur Vidarsson

    (Sanquin Research
    University of Amsterdam)

Abstract

Plasmodium falciparum erythrocyte membrane protein 1 (PfEMP1) family members mediate receptor- and tissue-specific sequestration of infected erythrocytes (IEs) in malaria. Antibody responses are a central component of naturally acquired malaria immunity. PfEMP1-specific IgG likely protects by inhibiting IE sequestration and through IgG-Fc Receptor (FcγR) mediated phagocytosis and killing of antibody-opsonized IEs. The affinity of afucosylated IgG to FcγRIIIa is up to 40-fold higher than fucosylated IgG, resulting in enhanced antibody-dependent cellular cytotoxicity. Most IgG in plasma is fully fucosylated, but afucosylated IgG is elicited in response to enveloped viruses and to paternal alloantigens during pregnancy. Here we show that naturally acquired PfEMP1-specific IgG is strongly afucosylated in a stable and exposure-dependent manner, and efficiently induces FcγRIIIa-dependent natural killer (NK) cell degranulation. In contrast, immunization with a subunit PfEMP1 (VAR2CSA) vaccine results in fully fucosylated specific IgG. These results have implications for understanding protective natural- and vaccine-induced immunity to malaria.

Suggested Citation

  • Mads Delbo Larsen & Mary Lopez-Perez & Emmanuel Kakra Dickson & Paulina Ampomah & Nicaise Tuikue Ndam & Jan Nouta & Carolien A. M. Koeleman & Agnes L. Hipgrave Ederveen & Benjamin Mordmüller & Ali Sal, 2021. "Afucosylated Plasmodium falciparum-specific IgG is induced by infection but not by subunit vaccination," Nature Communications, Nature, vol. 12(1), pages 1-10, December.
    • Handle: RePEc:nat:natcom:v:12:y:2021:i:1:d:10.1038_s41467-021-26118-w
    DOI: 10.1038/s41467-021-26118-w
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    Cited by:

    1. Mary Lopez-Perez & Zakaria Seidu & Mads Delbo Larsen & Wenjun Wang & Jan Nouta & Manfred Wuhrer & Gestur Vidarsson & Michael F. Ofori & Lars Hviid, 2025. "Acquisition of Fc-afucosylation of PfEMP1-specific IgG is age-dependent and associated with clinical protection against malaria," Nature Communications, Nature, vol. 16(1), pages 1-12, December.
    2. Aaron Gupta & Kevin S. Kao & Rachel Yamin & Deena A. Oren & Yehuda Goldgur & Jonathan Du & Pete Lollar & Eric J. Sundberg & Jeffrey V. Ravetch, 2023. "Mechanism of glycoform specificity and in vivo protection by an anti-afucosylated IgG nanobody," Nature Communications, Nature, vol. 14(1), pages 1-11, December.

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