Human Antibodies that Slow Erythrocyte Invasion Potentiate Malaria-Neutralizing Antibodies.
basic_science · Level V
Where this comes from
- Record sourced from PubMed, PMID 31204103.
- Also identified by DOI 10.1016/j.cell.2019.05.025 and PMC identifier 6602525.
- Licence recorded as CC BY.
- The licence permits redistribution, so the abstract is shown in full and the full text is available from the publisher.
Abstract
The Plasmodium falciparum reticulocyte-binding protein homolog 5 (PfRH5) is the leading target for next-generation vaccines against the disease-causing blood-stage of malaria. However, little is known about how human antibodies confer functional immunity against this antigen. We isolated a panel of human monoclonal antibodies (mAbs) against PfRH5 from peripheral blood B cells from vaccinees in the first clinical trial of a PfRH5-based vaccine. We identified a subset of mAbs with neutralizing activity that bind to three distinct sites and another subset of mAbs that are non-functional, or even antagonistic to neutralizing antibodies. We also identify the epitope of a novel group of non-neutralizing antibodies that significantly reduce the speed of red blood cell invasion by the merozoite, thereby potentiating the effect of all neutralizing PfRH5 antibodies as well as synergizing with antibodies targeting other malaria invasion proteins. Our results provide a roadmap for structure-guided vaccine development to maximize antibody efficacy against blood-stage malaria.
Medical subject headings
- Antibodies, Monoclonal
- Antibodies, Neutralizing
- Antibodies, Protozoan
- Erythrocytes
- Malaria Vaccines
- Malaria, Falciparum
- Plasmodium falciparum