Larsen M. D., Lopez-Perez M., Dickson E. K., Ampomah P., Tuikue Ndam Nicaise, Nouta J., Koeleman C. A. M., Ederveen A. L. H., Mordmuller B., Salanti A., Nielsen M. A., Massougbodji A., van der Schoot C. E., Ofori M. F., Wuhrer M., Hviid L., Vidarsson G. (2021). Afucosylated Plasmodium falciparum-specific IgG is induced by infection but not by subunit vaccination. Nature Communications, 12 (1), p. 5838 [10 p.].
Titre du document
Afucosylated Plasmodium falciparum-specific IgG is induced by infection but not by subunit vaccination
Année de publication
2021
Auteurs
Larsen M. D., Lopez-Perez M., Dickson E. K., Ampomah P., Tuikue Ndam Nicaise, Nouta J., Koeleman C. A. M., Ederveen A. L. H., Mordmuller B., Salanti A., Nielsen M. A., Massougbodji A., van der Schoot C. E., Ofori M. F., Wuhrer M., Hviid L., Vidarsson G.
Source
Nature Communications, 2021,
12 (1), p. 5838 [10 p.]
Here, Larsen et al. describe differences in Fc fucosylation of P. falciparum PfEMP1-specific IgG produced in response to natural infection versus VAR2CSA-type subunit vaccination, which leads to differences in the ability to induce Fc gamma RIIIa-dependent natural killer cell degranulation. 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 (Fc gamma R) mediated phagocytosis and killing of antibody-opsonized IEs. The affinity of afucosylated IgG to Fc gamma RIIIa 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 Fc gamma RIIIa-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.
Plan de classement
Santé : généralités [050]
;
Entomologie médicale / Parasitologie / Virologie [052]
Description Géographique
GHANA
Localisation
Fonds IRD [F B010083215]
Identifiant IRD
fdi:010083215
