title: Merozoite Antigens of Plasmodium falciparum Elicit Strain-Transcending Opsonizing Immunity.
abstract: It is unclear whether naturally acquired immunity to Plasmodium falciparum results from the acquisition of antibodies to multiple, diverse antigens or to fewer, highly conserved antigens. Moreover, the specific antibody functions required for malaria immunity are unknown, and hence informative immunological assays are urgently needed to address these knowledge gaps and guide vaccine development. In this study, we investigated whether merozoite-opsonizing antibodies are associated with protection from malaria in a strain-specific or strain-transcending manner by using a novel field isolate and an immune plasma-matched cohort from Papua New Guinea with our validated assay of merozoite phagocytosis. Highly correlated opsonization responses were observed across the 15 parasite strains tested, as were strong associations with protection (composite phagocytosis score across all strains in children uninfected at baseline: hazard ratio of 0.15, 95% confidence interval of 0.04 to 0.63). Opsonizing antibodies had a strong strain-transcending component, and the opsonization of transgenic parasites deficient for MSP3, MSP6, MSPDBL1, or P. falciparum MSP1-19 (PfMSP1-19) was similar to that of wild-type parasites. We have provided the first evidence that merozoite opsonization is predominantly strain transcending, and the highly consistent associations with protection against diverse parasite strains strongly supports the use of merozoite opsonization as a correlate of immunity for field studies and vaccine trials. These results demonstrate that conserved domains within merozoite antigens targeted by opsonization generate strain-transcending immune responses and represent promising vaccine candidates.
authors.affiliation: The Walter and Eliza Hall Institute of Medical Research, Parkville, Australia danika.hill@babraham.ac.uk.|Department of Medical Biology, University of Melbourne, Parkville, Australia.
authors.forename: Danika L
authors.initials: DL
authors.lastname: Hill
authors.affiliation: The Walter and Eliza Hall Institute of Medical Research, Parkville, Australia.|Department of Medical Biology, University of Melbourne, Parkville, Australia.|Research Centre for Infectious Diseases, School of Biological Sciences, University of Adelaide, Adelaide, Australia.
authors.forename: Danny W
authors.initials: DW
authors.lastname: Wilson
authors.affiliation: The Walter and Eliza Hall Institute of Medical Research, Parkville, Australia.|Department of Medical Biology, University of Melbourne, Parkville, Australia.
authors.forename: Natalia G
authors.initials: NG
authors.lastname: Sampaio
authors.affiliation: The Walter and Eliza Hall Institute of Medical Research, Parkville, Australia.|Department of Medical Biology, University of Melbourne, Parkville, Australia.
authors.forename: Emily M
authors.initials: EM
authors.lastname: Eriksson
authors.affiliation: The Walter and Eliza Hall Institute of Medical Research, Parkville, Australia.|Department of Medical Biology, University of Melbourne, Parkville, Australia.
authors.forename: Victoria
authors.initials: V
authors.lastname: Ryg-Cornejo
authors.affiliation: The Walter and Eliza Hall Institute of Medical Research, Parkville, Australia.|Department of Medical Biology, University of Melbourne, Parkville, Australia.
authors.forename: G L Abby
authors.initials: GLA
authors.lastname: Harrison
authors.affiliation: The Walter and Eliza Hall Institute of Medical Research, Parkville, Australia.|Department of Medical Biology, University of Melbourne, Parkville, Australia.
authors.forename: Alessandro D
authors.initials: AD
authors.lastname: Uboldi
authors.affiliation: The Walter and Eliza Hall Institute of Medical Research, Parkville, Australia.|Department of Medical Biology, University of Melbourne, Parkville, Australia.|Papua New Guinea Institute of Medical Research, Goroka and Madang, Papua New Guinea.
authors.forename: Leanne J
authors.initials: LJ
authors.lastname: Robinson
authors.affiliation: The Burnet Institute for Medical Research and Public Health, Melbourne, Australia.|Department of Microbiology, Monash University, Clayton, Australia.
authors.forename: James G
authors.initials: JG
authors.lastname: Beeson
authors.affiliation: Papua New Guinea Institute of Medical Research, Goroka and Madang, Papua New Guinea.
authors.forename: Peter
authors.initials: P
authors.lastname: Siba
authors.affiliation: The Walter and Eliza Hall Institute of Medical Research, Parkville, Australia.|Department of Medical Biology, University of Melbourne, Parkville, Australia.
authors.forename: Alan F
authors.initials: AF
authors.lastname: Cowman
authors.affiliation: The Walter and Eliza Hall Institute of Medical Research, Parkville, Australia.|Department of Medical Biology, University of Melbourne, Parkville, Australia.
authors.forename: Diana S
authors.initials: DS
authors.lastname: Hansen
authors.affiliation: The Walter and Eliza Hall Institute of Medical Research, Parkville, Australia.|Department of Medical Biology, University of Melbourne, Parkville, Australia.|Institute of Global Health, Barcelona, Spain.
authors.forename: Ivo
authors.initials: I
authors.lastname: Mueller
authors.affiliation: The Walter and Eliza Hall Institute of Medical Research, Parkville, Australia.|Department of Medical Biology, University of Melbourne, Parkville, Australia.|Australian Institute of Tropical Health and Medicine, James Cook University, Townsville, Australia.
authors.forename: Louis
authors.initials: L
authors.lastname: Schofield
mesh_terms: D000293:Adolescent; D000913:Antibodies, Protozoan / Q000097:blood / Q000276:immunology*; D000953:Antigens, Protozoan / Q000276:immunology*; D002648:Child; D002675:Child, Preschool; D006801:Humans; D016778:Malaria, Falciparum / Q000097:blood / Q000276:immunology* / Q000469:parasitology*; D052940:Merozoites / Q000276:immunology*; D009895:Opsonin Proteins / Q000276:immunology*; D063868:Patient Outcome Assessment; D010587:Phagocytosis / Q000276:immunology; D010963:Plasmodium falciparum / Q000276:immunology*
chemical_list: D000913:Antibodies, Protozoan; D000953:Antigens, Protozoan; D009895:Opsonin Proteins