Title |
Human Antibodies Fix Complement to Inhibit Plasmodium falciparum Invasion of Erythrocytes and Are Associated with Protection against Malaria
|
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Published in |
Immunity, March 2015
|
DOI | 10.1016/j.immuni.2015.02.012 |
Pubmed ID | |
Authors |
Michelle J. Boyle, Linda Reiling, Gaoqian Feng, Christine Langer, Faith H. Osier, Harvey Aspeling-Jones, Yik Sheng Cheng, Janine Stubbs, Kevin K.A. Tetteh, David J. Conway, James S. McCarthy, Ivo Muller, Kevin Marsh, Robin F. Anders, James G. Beeson |
Abstract |
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 as major targets. Complement fixation by antibodies was very strongly associated with protection from both clinical malaria and high-density parasitemia in a prospective longitudinal study of children. Ab-C' inhibitory activity could be induced by human immunization with a candidate merozoite surface-protein vaccine. Our findings demonstrate that human anti-malarial antibodies have evolved to function by fixing complement for potent invasion-inhibitory activity and protective immunity. |
X Demographics
Geographical breakdown
Country | Count | As % |
---|---|---|
Australia | 2 | 15% |
United Kingdom | 2 | 15% |
Iran, Islamic Republic of | 1 | 8% |
Portugal | 1 | 8% |
Unknown | 7 | 54% |
Demographic breakdown
Type | Count | As % |
---|---|---|
Members of the public | 5 | 38% |
Science communicators (journalists, bloggers, editors) | 5 | 38% |
Scientists | 2 | 15% |
Practitioners (doctors, other healthcare professionals) | 1 | 8% |
Mendeley readers
Geographical breakdown
Country | Count | As % |
---|---|---|
Portugal | 1 | <1% |
Kenya | 1 | <1% |
France | 1 | <1% |
Brazil | 1 | <1% |
Unknown | 298 | 99% |
Demographic breakdown
Readers by professional status | Count | As % |
---|---|---|
Student > Ph. D. Student | 57 | 19% |
Student > Master | 53 | 18% |
Student > Bachelor | 42 | 14% |
Researcher | 39 | 13% |
Student > Doctoral Student | 16 | 5% |
Other | 36 | 12% |
Unknown | 59 | 20% |
Readers by discipline | Count | As % |
---|---|---|
Agricultural and Biological Sciences | 70 | 23% |
Immunology and Microbiology | 59 | 20% |
Biochemistry, Genetics and Molecular Biology | 42 | 14% |
Medicine and Dentistry | 35 | 12% |
Pharmacology, Toxicology and Pharmaceutical Science | 7 | 2% |
Other | 29 | 10% |
Unknown | 60 | 20% |