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

Gaoqian Feng, Bruce D. Wines, Liriye Kurtovic, Jo-Anne Chan, Philippe Boeuf, Vanessa Mollard, Anton Cozijnsen, Damien R. Drew, Rob J. Center, Daniel L. Marshall, Sandra Chishimba, Geoffrey I. McFadden, Arlene E. Dent, Kiprotich Chelimo, Michelle J. Boyle, James W. Kazura, P. Mark Hogarth and James G. Beeson ()
Additional contact information
Gaoqian Feng: Burnet Institute for Medical Research and Public Health
Bruce D. Wines: Burnet Institute for Medical Research and Public Health
Liriye Kurtovic: Burnet Institute for Medical Research and Public Health
Jo-Anne Chan: Burnet Institute for Medical Research and Public Health
Philippe Boeuf: Burnet Institute for Medical Research and Public Health
Vanessa Mollard: The University of Melbourne
Anton Cozijnsen: The University of Melbourne
Damien R. Drew: Burnet Institute for Medical Research and Public Health
Rob J. Center: Burnet Institute for Medical Research and Public Health
Daniel L. Marshall: Burnet Institute for Medical Research and Public Health
Sandra Chishimba: Burnet Institute for Medical Research and Public Health
Geoffrey I. McFadden: The University of Melbourne
Arlene E. Dent: Case Western Reserve University
Kiprotich Chelimo: Maseno University
Michelle J. Boyle: Burnet Institute for Medical Research and Public Health
James W. Kazura: Case Western Reserve University
P. Mark Hogarth: Burnet Institute for Medical Research and Public Health
James G. Beeson: Burnet Institute for Medical Research and Public Health

Nature Communications, 2021, vol. 12, issue 1, 1-16

Abstract: 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.

Date: 2021
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Persistent link: https://EconPapers.repec.org/RePEc:nat:natcom:v:12:y:2021:i:1:d:10.1038_s41467-021-21998-4

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DOI: 10.1038/s41467-021-21998-4

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