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 - 2021/10/5
Y1 - 2021/10/5
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.
KW - Antibodies, Protozoan/metabolism
KW - Antigens, Protozoan/immunology
KW - Female
KW - Humans
KW - Immunoglobulin G/metabolism
KW - Malaria, Falciparum/immunology
KW - Plasmodium falciparum/metabolism
KW - Pregnancy
KW - Vaccination
UR - http://www.scopus.com/inward/record.url?scp=85116357207&partnerID=8YFLogxK
U2 - 10.1038/s41467-021-26118-w
DO - 10.1038/s41467-021-26118-w
M3 - Journal article
C2 - 34611164
SN - 2041-1722
VL - 12
SP - 5838
JO - Nature Communications
JF - Nature Communications
IS - 1
M1 - 5838
ER -