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Title: Antibodies against a Plasmodium falciparum RON12 inhibit merozoite invasion into erythrocytes
Authors: Daisuke Ito
Eizo Takashima
Tsutomu Yamasaki
Shinya Hatano
Tomoyuki Hasegawa
Kazutoyo Miura
Masayuki Morita
Amporn Thongkukiatkul
Mahamadou Diakite
Carole A. Long
Jetsumon Sattabongkot
Rachanee Udomsangpetch
Hideyuki Iriko
Tomoko Ishino
Takafumi Tsuboi
Shujitsu University
Kobe University School of Medicine
National Institute of Allergy and Infectious Diseases
Mahidol University
Tottori University
Burapha University
Ehime University
University of Sciences
Keywords: Immunology and Microbiology;Medicine
Issue Date: 1-Feb-2019
Citation: Parasitology International. Vol.68, No.1 (2019), 87-91
Abstract: © 2018 Elsevier B.V. Proteins coating Plasmodium merozoite surface and secreted from its apical organelles are considered as promising vaccine candidates for blood-stage malaria. The rhoptry neck protein 12 of Plasmodium falciparum (PfRON12) was recently reported as a protein specifically expressed in schizonts and localized to the rhoptry neck of merozoites. Here, we assessed its potential as a vaccine candidate. We expressed a recombinant PfRON12 protein by a wheat germ cell-free system to obtain anti-PfRON12 antibody. Immunoblot analysis of schizont lysates detected a single band at approximately 40 kDa under reducing conditions, consistent with the predicted molecular weight. Additionally, anti-PfRON12 antibody recognized a single band around 80 kDa under non-reducing conditions, suggesting native PfRON12 forms a disulfide-bond-mediated multimer. Immunofluorescence assay and immunoelectron microscopy revealed that PfRON12 localized to the rhoptry neck of merozoites in schizonts and to the surface of free merozoites. The biological activity of anti-PfRON12 antibody was tested by in vitro growth inhibition assay (GIA), and the rabbit antibodies significantly inhibited merozoite invasion of erythrocytes. We then investigated whether PfRON12 is immunogenic in P. falciparum-infected individuals. The sera from P. falciparum infected individuals in Thailand and Mali reacted with the recombinant PfRON12. Furthermore, human anti-PfRON12 antibodies affinity-purified from Malian serum samples inhibited merozoite invasion of erythrocytes in vitro. Moreover, pfron12 is highly conserved with only 4 non-synonymous mutations in the coding sequence from approximately 200 isolates deposited in PlasmoDB. These results suggest that PfRON12 might be a potential blood-stage vaccine candidate antigen against P. falciparum.
ISSN: 18730329
Appears in Collections:Scopus 2019

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