Afucosylated Plasmodium falciparum-specific IgG is induced by infection but not by subunit vaccination
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Afucosylated Plasmodium falciparum-specific IgG is induced by infection but not by subunit vaccination. / Larsen, Mads Delbo; Lopez-Perez, Mary; Dickson, Emmanuel Kakra; Ampomah, Paulina; Tuikue Ndam, Nicaise; Nouta, Jan; Koeleman, Carolien A M; Ederveen, Agnes L Hipgrave; Mordmüller, Benjamin; Salanti, Ali; Nielsen, Morten Agertoug; Massougbodji, Achille; van der Schoot, C Ellen; Ofori, Michael F; Wuhrer, Manfred; Hviid, Lars; Vidarsson, Gestur.
In: Nature Communications, Vol. 12, 5838, 2021.Research output: Contribution to journal › Journal article › Research › peer-review
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TY - JOUR
T1 - Afucosylated Plasmodium falciparum-specific IgG is induced by infection but not by subunit vaccination
AU - Larsen, Mads Delbo
AU - Lopez-Perez, Mary
AU - Dickson, Emmanuel Kakra
AU - Ampomah, Paulina
AU - Tuikue Ndam, Nicaise
AU - Nouta, Jan
AU - Koeleman, Carolien A M
AU - Ederveen, Agnes L Hipgrave
AU - Mordmüller, Benjamin
AU - Salanti, Ali
AU - Nielsen, Morten Agertoug
AU - Massougbodji, Achille
AU - van der Schoot, C Ellen
AU - Ofori, Michael F
AU - Wuhrer, Manfred
AU - Hviid, Lars
AU - Vidarsson, Gestur
N1 - © 2021. The Author(s).
PY - 2021
Y1 - 2021
N2 - 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.
AB - 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.
U2 - 10.1038/s41467-021-26118-w
DO - 10.1038/s41467-021-26118-w
M3 - Journal article
C2 - 34611164
VL - 12
JO - Nature Communications
JF - Nature Communications
SN - 2041-1723
M1 - 5838
ER -
ID: 281284752