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Mechanisms and targets of Fcγ-receptor mediated immunity to malaria sporozoites

Authors :
P. Mark Hogarth
Damien R. Drew
Bruce D. Wines
Kiprotich Chelimo
Liriye Kurtovic
Anton Cozijnsen
Michelle J. Boyle
Daniel L Marshall
Gaoqian Feng
Jo-Anne Chan
James W. Kazura
Philippe Boeuf
Arlene E. Dent
Geoffrey I. McFadden
Sandra Chishimba
James G. Beeson
Vanessa Mollard
Source :
Nature Communications, Nature Communications, Vol 12, Iss 1, Pp 1-16 (2021)
Publication Year :
2021
Publisher :
Nature Publishing Group UK, 2021.

Abstract

A highly protective vaccine will greatly facilitate achieving and sustaining malaria elimination. Understanding mechanisms of antibody-mediated immunity is crucial for developing vaccines with high efficacy. Here, we identify key roles in humoral immunity for Fcγ-receptor (FcγR) interactions and opsonic phagocytosis of sporozoites. We identify a major role for neutrophils in mediating phagocytic clearance of sporozoites in peripheral blood, whereas monocytes contribute a minor role. Antibodies also promote natural killer cell activity. Mechanistically, antibody interactions with FcγRIII appear essential, with FcγRIIa also required for maximum activity. All regions of the circumsporozoite protein are targets of functional antibodies against sporozoites, and N-terminal antibodies have more activity in some assays. Functional antibodies are slowly acquired following natural exposure to malaria, being present among some exposed adults, but uncommon among children. Our findings reveal targets and mechanisms of immunity that could be exploited in vaccine design to maximize efficacy.<br />Antibodies plays critical roles in the adaptive immune response to infectious agents including malaria. Here the authors defined antibody interactions with -Fcγ-receptors expressed on immune cells with sporozoites of Plasmodium falciparum, and identified specific target epitopes of antibodies.

Details

Language :
English
ISSN :
20411723
Volume :
12
Database :
OpenAIRE
Journal :
Nature Communications
Accession number :
edsair.doi.dedup.....482f3169e8a54e29800470b5acee0008