IDEAS home Printed from https://ideas.repec.org/a/nat/natcom/v12y2021i1d10.1038_s41467-021-26118-w.html
   My bibliography  Save this article

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
    as

    Download full text from publisher

    File URL: https://www.nature.com/articles/s41467-021-26118-w
    File Function: Abstract
    Download Restriction: no
    File URL: https://libkey.io/10.1038/s41467-021-26118-w?utm_source=ideas
    LibKey link: if access is restricted and if your library uses this service, LibKey will redirect you to where you can use your library subscription to access this item
    ---><---

    Citations

    Citations are extracted by the CitEc Project, subscribe to its RSS feed for this item.
    as


    Cited by:

    1. 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.

    More about this item

    Statistics

    Access and download statistics

    Corrections

    All material on this site has been provided by the respective publishers and authors. You can help correct errors and omissions. When requesting a correction, please mention this item's handle: RePEc:nat:natcom:v:12:y:2021:i:1:d:10.1038_s41467-021-26118-w. See general information about how to correct material in RePEc.

    If you have authored this item and are not yet registered with RePEc, we encourage you to do it here. This allows to link your profile to this item. It also allows you to accept potential citations to this item that we are uncertain about.

    We have no bibliographic references for this item. You can help adding them by using this form .

    If you know of missing items citing this one, you can help us creating those links by adding the relevant references in the same way as above, for each refering item. If you are a registered author of this item, you may also want to check the "citations" tab in your RePEc Author Service profile, as there may be some citations waiting for confirmation.

    For technical questions regarding this item, or to correct its authors, title, abstract, bibliographic or download information, contact: Sonal Shukla or Springer Nature Abstracting and Indexing (email available below). General contact details of provider: http://www.nature.com .

    Please note that corrections may take a couple of weeks to filter through the various RePEc services.

    IDEAS is a RePEc service. RePEc uses bibliographic data supplied by the respective publishers.