Journal article

Mechanisms and targets of Fc gamma-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 McFadden, Arlene E Dent, Kiprotich Chelimo, Michelle J Boyle, James W Kazura, P Mark Hogarth, James G Beeson



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 pro..

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Awarded by NIH International Centers for Excellence in Malaria Research

Funding Acknowledgements

We thank the study participants and staff of the Kenyan Medical Research Institute for samples from Chulaimbo cohort and Kanyawegi cohorts. P. falciparum sporozoites, and mAb 2H8 were kindly provided by PATH Malaria Vaccine Initiative (MVI). The mAb 3D11 and hybridoma were kindly provided by Miguel Prudencio of the Instituto de Medicina Molecular. P. berghei parasites expressing P. falciparum CSP were provided by Chris Janse, Shahid Khan, and Hans Kroeze of Leiden University Medical Center. Covalent coupling of antigen to fluorescent beads was greatly supported by Paul Ramsland of RMIT, Paul Sanders of Burnet Institute and Geoffrey Pietersz of the Baker Heart and Diabetes Institute. We also thank Michelle Wong of Burnet Institute for being our phlebotomists and Emily Locke for helpful feedback and advice. This study was also supported by AMREP Flow cytometry core facility. This work was supported by the National Health and Medical Research Council (NHMRC) of Australia (Program Grant and Senior Research Fellowship to JG Beeson; Project Grants to J.G.B., GI McFadden, and PM Hogarth; Career Development Fellowship to M.J.B.), PATH-MVI (grant to J.G.B.), CASS Foundation (grant to G.F.), Australian Research Council Laureate Fellowship to GI McFadden, and NIH International Centers for Excellence in Malaria Research (U19AI129326). The Burnet Institute is supported by the NHMRC for Independent Research Institutes Infrastructure Support Scheme and the Victorian State Government Operational Infrastructure Support. J.G.B., G.F., M.J.B., J.A.C., SC and L.K. are members of the NHMRC Australian Centre for Research Excellence in Malaria Elimination.