Human Antibodies Fix Complement to Inhibit Plasmodium falciparum Invasion of Erythrocytes and Are Associated with Protection against Malaria
Michelle J Boyle, Linda Reiling, Gaoqian Feng, Christine Langer, Faith H Osier, Harvey Aspeling-Jones, Yik Sheng Cheng, Janine Stubbs, Kevin KA Tetteh, David J Conway, James S McCarthy, Ivo Muller, Kevin Marsh, Robin F Anders, James G Beeson
Immunity | CELL PRESS | Published : 2015
Antibodies play major roles in immunity to malaria; however, a limited understanding of mechanisms mediating protection is a major barrier to vaccine development. We have demonstrated that acquired human anti-malarial antibodies promote complement deposition on the merozoite to mediate inhibition of erythrocyte invasion through C1q fixation and activation of the classical complement pathway. Antibody-mediated complement-dependent (Ab-C') inhibition was the predominant invasion-inhibitory activity of human antibodies; most antibodies were non-inhibitory without complement. Inhibitory activity was mediated predominately via C1q fixation, and merozoite surface proteins 1 and 2 were identified a..View full abstract
Awarded by Medical Research Council
RBCs and serum for parasite culture were provided by the Australian Red Cross Blood Bank (Melbourne). We thank the following people for reagents: D. Drew and A. Hodder (AMA1 antibodies), R. Coppel and B. Cooke (MSP4 antigen and MSP4 antibodies), and B. Crabb and P. Gilson (MSP1-19 antibodies). Funding was provided by the National Health and Medical Research Council of Australia (program grant to J.G.B.; Infrastructure for Research Institutes Support Scheme grant and research fellowships to J.G.B. and J.S.M.), the Australian Research Council (Future Fellowship to J.G.B.), a Victorian State Government Operational Infrastructure Support grant, the Queensland Government (Medical Research Fellowship to J.S.M.), the Australian Government (PhD scholarship to M.J.B.), and the University of Melbourne Department of Medicine, Dentistry, and Health Sciences (PhD top-up award to M.J.B.). The MSP2 phase 1 vaccine trial was funded by PATH Malaria Vaccine Initiative. The funders had no role in the study design, data collection and analysis, decision to publish, or preparation of the manuscript. We thank D. Wilson and P. Jagannathan for critical reading of the manuscript and Kristina Persson for helpful discussions. This paper is published with permission from the director of KEMRI.