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 - Funding Information: We are grateful to all the individuals donating blood samples for this study, and to the scientists and health workers participating in the studies for which they were originally collected. We thank Michael Theisen (University of Copenhagen and Statens Serumin-stitut) for GLURP antigen and GLURP-reactive IgG preparation, and Bruce Walcheck and Geoff Hart (University of Minnesota) for the NK92-CD16a cell line. We also acknowledge Erik de Graaf (Sanquin Research) for optimization of the analysis pipelines used in this study, done in relation to previous projects. The study was funded by the Landsteiner Foundation for Blood Transfusion Research grant number 1721 and the Danish International Development Agency (Danida), 12-081RH and 17-02-KU. The PAMVAC study (ClinicalTrials.gov ID NCT02647489) was sponsored by the Uni-versitätsklinikum Tübingen and funded by the European Union Seventh Framework Programme (FP7-HEALTH-2012-INNOVATION; under grant agreement 304815), the Danish Advanced Technology Foundation (under grant number 005-2011-1), and a Medium Scale Collaborative Project supported by the German Federal Ministry of Education and Research (Bundesministerium für Bildung und Forschung) through EVI, KfW, and Irish Aid. The funders had no role in study design, data collection and analysis, decision to publish, or preparation of the manuscript. Publisher Copyright: © 2021, The Author(s).
PY - 2021/12/1
Y1 - 2021/12/1
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.
UR - http://www.scopus.com/inward/record.url?scp=85116357207&partnerID=8YFLogxK
U2 - https://doi.org/10.1038/s41467-021-26118-w
DO - https://doi.org/10.1038/s41467-021-26118-w
M3 - Article
C2 - 34611164
SN - 2041-1723
VL - 12
JO - Nature communications
JF - Nature communications
IS - 1
M1 - 5838
ER -