title: Antibodies to the Plasmodium falciparum Proteins MSPDBL1 and MSPDBL2 Opsonize Merozoites, Inhibit Parasite Growth, and Predict Protection From Clinical Malaria.
abstract: Increasing evidence suggests that antibodies against merozoite surface proteins (MSPs) play an important role in clinical immunity to malaria. Two unusual members of the MSP-3 family, merozoite surface protein duffy binding-like (MSPDBL)1 and MSPDBL2, have been shown to be extrinsically associated to MSP-1 on the parasite surface. In addition to a secreted polymorphic antigen associated with merozoite (SPAM) domain characteristic of MSP-3 family members, they also contain Duffy binding-like (DBL) domain and were found to bind to erythrocytes, suggesting that they play a role in parasite invasion. Antibody responses to these proteins were investigated in a treatment-reinfection study conducted in an endemic area of Papua New Guinea to determine their contribution to naturally acquired immunity. Antibodies to the SPAM domains of MSPDBL1 and MSPDBL2 as well as the DBL domain of MSPDBL1 were found to be associated with protection from Plasmodium falciparum clinical episodes. Moreover, affinity-purified anti-MSPDBL1 and MSPDBL2 were found to inhibit in vitro parasite growth and had strong merozoite opsonizing capacity, suggesting that protection targeting these antigens results from ≥2 distinct effector mechanisms. Together these results indicate that MSPDBL1 and MSPDBL2 are important targets of naturally acquired immunity and might constitute potential vaccine candidates.
authors: The Walter and Eliza Hall Institute of Medical Research Department of Medical Biology, University of Melbourne, Parkville, Victoria.
authors: Chris Y H
authors: CY
authors: Chiu
authors: The Walter and Eliza Hall Institute of Medical Research Department of Medical Biology, University of Melbourne, Parkville, Victoria.
authors: Anthony N
authors: AN
authors: Hodder
authors: The Walter and Eliza Hall Institute of Medical Research Department of Medical Biology, University of Melbourne, Parkville, Victoria.
authors: Clara S
authors: CS
authors: Lin
authors: The Walter and Eliza Hall Institute of Medical Research Department of Medical Biology, University of Melbourne, Parkville, Victoria.
authors: Danika L
authors: DL
authors: Hill
authors: The Walter and Eliza Hall Institute of Medical Research.
authors: Connie S N
authors: CS
authors: Li Wai Suen
authors: The Walter and Eliza Hall Institute of Medical Research Australian Institute of Tropical Health and Medicine, James Cook University, Douglas, Queensland, Australia.
authors: Louis
authors: L
authors: Schofield
authors: Vector Borne Disease Unit, Papua New Guinea Institute of Medical Research, Eastern Highlands Province, Goroka.
authors: Peter M
authors: PM
authors: Siba
authors: The Walter and Eliza Hall Institute of Medical Research Barcelona Center for International Health, University of Barcelona, Spain.
authors: Ivo
authors: I
authors: Mueller
authors: The Walter and Eliza Hall Institute of Medical Research Department of Medical Biology, University of Melbourne, Parkville, Victoria.
authors: Alan F
authors: AF
authors: Cowman
authors: The Walter and Eliza Hall Institute of Medical Research Department of Medical Biology, University of Melbourne, Parkville, Victoria.
authors: Diana S
authors: DS
authors: Hansen
mesh_terms: D000293:Adolescent; D000913:Antibodies, Protozoan / Q000097:blood / Q000276:immunology*; D002648:Child; D002675:Child, Preschool; D015331:Cohort Studies; D006801:Humans; D007074:Immunoglobulin G / Q000097:blood / Q000276:immunology; D015994:Incidence; D053208:Kaplan-Meier Estimate; D016778:Malaria, Falciparum / Q000453:epidemiology / Q000276:immunology* / Q000469:parasitology; D008565:Membrane Proteins / Q000276:immunology; D010219:Papua New Guinea / Q000453:epidemiology; D010963:Plasmodium falciparum / Q000276:immunology*; D015800:Protozoan Proteins / Q000276:immunology*; D011994:Recombinant Proteins
chemical_list: D000913:Antibodies, Protozoan; D007074:Immunoglobulin G; D008565:Membrane Proteins; D015800:Protozoan Proteins; D011994:Recombinant Proteins
keywords: MSPDBL1; MSPDBL2; Plasmodium falciparum; antibodies; immunity; malaria