title: Plasmodium vivax gametocyte proteins, Pvs48/45 and Pvs47, induce transmission-reducing antibodies by DNA immunization.
abstract: Malaria transmission-blocking vaccines (TBV) aim to interfere with the development of the malaria parasite in the mosquito vector, and thus prevent spread of transmission in a community. To date three TBV candidates have been identified in Plasmodium vivax; namely, the gametocyte/gamete protein Pvs230, and the ookinete surface proteins Pvs25 and Pvs28. The Plasmodium falciparum gametocyte/gamete stage proteins Pfs48/45 and Pfs47 have been studied as TBV candidates, and Pfs48/45 shown to induce transmission-blocking antibodies, but the candidacy of their orthologs in P. vivax, Pvs48/45 (PVX_083235) and Pvs47 (PVX_083240), for vivax TBV have not been tested. Herein we investigated whether targeting Pvs48/45 and Pvs47 can inhibit parasite transmission to mosquitoes, using P. vivax isolates obtained in Thailand. Mouse antisera directed against the products from plasmids expressing Pvs48/45 and Pvs47 detected proteins of approximately 45- and 40-kDa, respectively, in the P. vivax gametocyte lysate, by Western blot analysis under non-reducing conditions. In immunofluorescence assays Pvs48/45 was detected predominantly on the surface and Pvs47 was detected in the cytoplasm of gametocytes. Membrane feeding transmission assays demonstrated that anti-Pvs48/45 and -Pvs47 mouse sera significantly reduced the number of P. vivax oocysts developing in the mosquito midgut. Limited amino acid polymorphism of these proteins was observed among 27 P. vivax isolates obtained from Thailand, Vanuatu, and Colombia; suggesting that polymorphism may not be an impediment for the utilization of Pvs48/45 and Pvs47 as TBV antigens. In one Thai isolate we found that the fourth cysteine residue in the Pvs47 cysteine-rich domain (CRD) III (amino acid position 337) is substituted to phenylalanine. However, antibodies targeting Pvs47 CRDI-III showed a significant transmission-reducing activity against this isolate, suggesting that this substitution in Pvs47 was not critical for recognition by the generated antibodies. In conclusion, our results indicate that Pvs48/45 and Pvs47 are potential transmission-blocking vaccine candidates of P. vivax.
authors.affiliation: Division of Molecular Parasitology, Proteo-Science Center, Ehime University, Shitsukawa, Toon, Ehime 791-0295, Japan.
authors.forename: Mayumi
authors.initials: M
authors.lastname: Tachibana
authors.affiliation: Department of Entomology, Armed Forces Research Institute of Medical Sciences, Bangkok 10400, Thailand.
authors.forename: Nantavadee
authors.initials: N
authors.lastname: Suwanabun
authors.affiliation: Department of Protozoology, Institute of Tropical Medicine (NEKKEN), Nagasaki University, Sakamoto, Nagasaki 852-8523, Japan.
authors.forename: Osamu
authors.initials: O
authors.lastname: Kaneko
authors.affiliation: Department of Parasitology, Faculty of Health Sciences, Kobe University Graduate School of Health Sciences, Kobe 654-0142, Japan.
authors.forename: Hideyuki
authors.initials: H
authors.lastname: Iriko
authors.affiliation: Division of Medical Zoology, Faculty of Medicine, Tottori University, Yonago, Tottori 683-8503, Japan.
authors.forename: Hitoshi
authors.initials: H
authors.lastname: Otsuki
authors.affiliation: Department of Entomology, Armed Forces Research Institute of Medical Sciences, Bangkok 10400, Thailand.
authors.forename: Jetsumon
authors.initials: J
authors.lastname: Sattabongkot
authors.affiliation: Department of Parasitology, Osaka City University Graduate School of Medicine, Osaka 545-8585, Japan; Island Malaria Group, Department of Microbiology, Tumor and Cell Biology, Karolinska Institutet, SE-17177 Stockholm, Sweden.
authors.forename: Akira
authors.initials: A
authors.lastname: Kaneko
authors.affiliation: Malaria Vaccine and Drug Development Center, Cali AA 25574, Colombia.
authors.forename: Socrates
authors.initials: S
authors.lastname: Herrera
authors.affiliation: Division of Molecular Parasitology, Proteo-Science Center, Ehime University, Shitsukawa, Toon, Ehime 791-0295, Japan. Electronic address: torii@m.ehime-u.ac.jp.
authors.forename: Motomi
authors.initials: M
authors.lastname: Torii
authors.affiliation: Division of Malaria Research, Proteo-Science Center, Ehime University, Matsuyama, Ehime 790-8577, Japan. Electronic address: tsuboi.takafumi.mb@ehime-u.ac.jp.
authors.forename: Takafumi
authors.initials: T
authors.lastname: Tsuboi
mesh_terms: D019943:Amino Acid Substitution; D000818:Animals; D000913:Antibodies, Protozoan / Q000276:immunology*; D000953:Antigens, Protozoan / Q000737:chemistry / Q000235:genetics / Q000276:immunology*; D005260:Female; D006801:Humans; D017780:Malaria Vaccines / Q000008:administration & dosage / Q000235:genetics / Q000276:immunology*; D016780:Malaria, Vivax / Q000517:prevention & control* / Q000635:transmission; D051379:Mice; D010455:Peptides / Q000235:genetics / Q000276:immunology; D010966:Plasmodium vivax / Q000235:genetics / Q000276:immunology*; D011110:Polymorphism, Genetic; D051381:Rats; D014611:Vaccination; D019444:Vaccines, DNA / Q000008:administration & dosage / Q000276:immunology*
chemical_list: D000913:Antibodies, Protozoan; D000953:Antigens, Protozoan; D017780:Malaria Vaccines; D010455:Peptides; D019444:Vaccines, DNA
keywords: DNA vaccine; Gametocyte; Malaria; Plasmodium vivax; Polymorphism; Transmission-blocking vaccine