Neutralization of Plasmodium falciparum merozoites by antibodies against PfRH5.

Journal article

There is intense interest in induction and characterization of strain-transcending neutralizing Ab against antigenically variable human pathogens. We have recently identified the human malaria parasite Plasmodium falciparum reticulocyte-binding protein homolog 5 (PfRH5) as a target of broadly neutralizing Abs, but there is little information regarding the functional mechanism(s) of Ab-mediated neutralization. In this study, we report that vaccine-induced polyclonal anti-PfRH5 Abs inhibit the tight attachment of merozoites to erythrocytes and are capable of blocking the interaction of PfRH5 with its receptor basigin. Furthermore, by developing anti-PfRH5 mAbs, we provide evidence of the following: 1) the ability to block the PfRH5-basigin interaction in vitro is predictive of functional activity, but absence of blockade does not predict absence of functional activity; 2) neutralizing mAbs bind spatially related epitopes on the folded protein, involving at least two defined regions of the PfRH5 primary sequence; 3) a brief exposure window of PfRH5 is likely to necessitate rapid binding of Ab to neutralize parasites; and 4) intact bivalent IgG contributes to but is not necessary for parasite neutralization. These data provide important insight into the mechanisms of broadly neutralizing anti-malaria Abs and further encourage anti-PfRH5-based malaria prevention efforts.

Authors: Douglas, A; Williams, A; Knuepfer, E; Illingworth, J; Furze, J

• Publication status: Published
• Journal: Journal of Immunology
• Volume: 192
• Issue: 1
• Pages: 245-258
• Publication date: 2014-01-01
• DOI: 10.4049/jimmunol.1302045
• EISSN: 1550-6606
• ISSN: 0022-1767
• Language: English
• Keywords: Amino Acid Sequence; Merozoites; Carrier Proteins; Kinetics; Epitope Mapping; Malaria Vaccines; Rabbits; Mice; Epitopes; Plasmodium falciparum; Protein Binding; Humans; Neutralization Tests; Antibodies, Monoclonal; Animals; Malaria, Falciparum; Antibodies, Neutralizing; Antibodies, Protozoan; Erythrocytes