title: Bacterially expressed full-length recombinant Plasmodium falciparum RH5 protein binds erythrocytes and elicits potent strain-transcending parasite-neutralizing antibodies.
abstract: Plasmodium falciparum reticulocyte binding-like homologous protein 5 (PfRH5) is an essential merozoite ligand that binds with its erythrocyte receptor, basigin. PfRH5 is an attractive malaria vaccine candidate, as it is expressed by a wide number of P. falciparum strains, cannot be genetically disrupted, and exhibits limited sequence polymorphisms. Viral vector-induced PfRH5 antibodies potently inhibited erythrocyte invasion. However, it has been a challenge to generate full-length recombinant PfRH5 in a bacterial-cell-based expression system. In this study, we have produced full-length recombinant PfRH5 in Escherichia coli that exhibits specific erythrocyte binding similar to that of the native PfRH5 parasite protein and also, importantly, elicits potent invasion-inhibitory antibodies against a number of P. falciparum strains. Antibasigin antibodies blocked the erythrocyte binding of both native and recombinant PfRH5, further confirming that they bind with basigin. We have thus successfully produced full-length PfRH5 as a functionally active erythrocyte binding recombinant protein with a conformational integrity that mimics that of the native parasite protein and elicits potent strain-transcending parasite-neutralizing antibodies. P. falciparum has the capability to develop immune escape mechanisms, and thus, blood-stage malaria vaccines that target multiple antigens or pathways may prove to be highly efficacious. In this regard, antibody combinations targeting PfRH5 and other key merozoite antigens produced potent additive inhibition against multiple worldwide P. falciparum strains. PfRH5 was immunogenic when immunized with other antigens, eliciting potent invasion-inhibitory antibody responses with no immune interference. Our results strongly support the development of PfRH5 as a component of a combination blood-stage malaria vaccine.
authors.affiliation: Malaria Group, International Centre for Genetic Engineering and Biotechnology (ICGEB), New Delhi, India.
authors.forename: K Sony
authors.initials: KS
authors.lastname: Reddy
authors.forename: Alok K
authors.initials: AK
authors.lastname: Pandey
authors.forename: Hina
authors.initials: H
authors.lastname: Singh
authors.forename: Tajali
authors.initials: T
authors.lastname: Sahar
authors.forename: Amlabu
authors.initials: A
authors.lastname: Emmanuel
authors.forename: Chetan E
authors.initials: CE
authors.lastname: Chitnis
authors.forename: Virander S
authors.initials: VS
authors.lastname: Chauhan
authors.forename: Deepak
authors.initials: D
authors.lastname: Gaur
mesh_terms: D000818:Animals; D057134:Antibodies, Neutralizing / Q000276:immunology*; D000913:Antibodies, Protozoan / Q000276:immunology*; D051926:Basigin / Q000276:immunology* / Q000378:metabolism; D002352:Carrier Proteins / Q000276:immunology* / Q000378:metabolism; D004912:Erythrocytes / Q000276:immunology* / Q000469:parasitology; D004926:Escherichia coli; D006790:Host-Parasite Interactions / Q000276:immunology*; D057131:Immune Evasion / Q000276:immunology; D017780:Malaria Vaccines / Q000276:immunology*; D016778:Malaria, Falciparum / Q000276:immunology; D051379:Mice; D008807:Mice, Inbred BALB C; D010963:Plasmodium falciparum / Q000276:immunology*; D011485:Protein Binding / Q000276:immunology; D011994:Recombinant Proteins / Q000276:immunology
chemical_list: D057134:Antibodies, Neutralizing; D000913:Antibodies, Protozoan; C497887:Bsg protein, mouse; D002352:Carrier Proteins; D017780:Malaria Vaccines; C531020:RH5 protein, Plasmodium falciparum; D011994:Recombinant Proteins; D051926:Basigin