title: Antibodies against a Plasmodium falciparum antigen PfMSPDBL1 inhibit merozoite invasion into human erythrocytes.
abstract: One approach to develop a malaria blood-stage vaccine is to target proteins that play critical roles in the erythrocyte invasion of merozoites. The merozoite surface proteins (MSPs) and the erythrocyte-binding antigens (EBAs) are considered promising vaccine candidates, for they are known to play important roles in erythrocyte invasion and are exposed to host immune system. Here we focused on a Plasmodium falciparum antigen, PfMSPDBL1 (encoded by PF10_0348 gene) that is a member of the MSP3 family and has both Duffy binding-like (DBL) domain and secreted polymorphic antigen associated with merozoites (SPAM) domain. Therefore, we aimed to characterize PfMSPDBL1 as a vaccine candidate. Recombinant full-length protein (rFL) of PfMSPDBL1 was synthesized by a wheat germ cell-free system, and rabbit antiserum was raised against rFL. We show that rabbit anti-PfMSPDBL1 antibodies inhibited erythrocyte invasion of wild type parasites in vitro in a dose dependent manner, and the specificity of inhibitory activity was confirmed using PfMSPDBL1 knockout parasites. Pre-incubation of the anti-PfMSPDBL1 antibodies with the recombinant SPAM domain had no effect on the inhibitory activity suggesting that antibodies to this region were not involved. In addition, antibodies to rFL were elicited by P. falciparum infection in malaria endemic area, suggesting the PfMSLDBL1 is immunogenic to humans. Our results suggest that PfMSPDBL1 is a novel blood-stage malaria vaccine candidate.
authors.affiliation: Cell-Free Science and Technology Research Center and Ehime University, Matsuyama, Ehime 790-8577, Japan.
authors.forename: Hirokazu
authors.initials: H
authors.lastname: Sakamoto
authors.forename: Satoru
authors.initials: S
authors.lastname: Takeo
authors.forename: Alexander G
authors.initials: AG
authors.lastname: Maier
authors.forename: Jetsumon
authors.initials: J
authors.lastname: Sattabongkot
authors.forename: Alan F
authors.initials: AF
authors.lastname: Cowman
authors.forename: Takafumi
authors.initials: T
authors.lastname: Tsuboi
mesh_terms: D000818:Animals; D000913:Antibodies, Protozoan / Q000096:biosynthesis / Q000276:immunology*; D000918:Antibody Specificity; D000953:Antigens, Protozoan / Q000276:immunology*; D002474:Cell-Free System; D003429:Cross Reactions; D004912:Erythrocytes / Q000469:parasitology*; D006801:Humans; D007074:Immunoglobulin G / Q000096:biosynthesis / Q000276:immunology; D017780:Malaria Vaccines / Q000276:immunology; D052940:Merozoites / Q000276:immunology / Q000502:physiology*; D009500:Neutralization Tests; D010957:Plasmids; D010963:Plasmodium falciparum / Q000254:growth & development / Q000276:immunology*; D015800:Protozoan Proteins / Q000276:immunology*; D011817:Rabbits; D011994:Recombinant Proteins / Q000096:biosynthesis / Q000276:immunology
chemical_list: D000913:Antibodies, Protozoan; D000953:Antigens, Protozoan; D007074:Immunoglobulin G; D017780:Malaria Vaccines; D015800:Protozoan Proteins; D011994:Recombinant Proteins