title: Adenovirus-vectored Plasmodium vivax ookinete surface protein, Pvs25, as a potential transmission-blocking vaccine.
abstract: Adjuvants or delivery vehicles are essential components to expedite malaria vaccine development. In this study, replication-defective human adenovirus serotype 5 (rAd) was genetically engineered to express the Plasmodium vivax ookinete surface protein (OSP), Pvs25 (AdPvs25). BALB/c mice immunized with the AdPvs25 through various routes including intramuscular, subcutaneous and intranasal routes were analyzed for induction of antigen-specific transmission-blocking immunity. Parenteral but not mucosal immunization induced high serum immunoglobulin G (IgG) responses specific to P. vivax ookinetes isolated from P. vivax volunteer patients from Thailand. The membrane feeding assay revealed that antisera conferred a transmission blockade of up to 99% reduction in the average oocyst numbers per mosquito, while immunization with a rAd expressing Pfs25 from Plasmodium falciparum, a homolog of Pvs25, conferred only a background level of blockade, suggesting that a species-specific transmission-blocking immunity was induced. Vaccine efficacy of AdPvs25 was slightly higher than to a recombinant Pvs25 protein mixed with aluminum hydroxide, but less efficacious than the protein emulsified with incomplete Freund's adjuvant. This study, the first preclinical evaluation of adenovirus-vectored malaria OSPs, implicates a potential inclusion of malaria transmission-blocking vaccine antigens in viral vector systems.
authors.affiliation: Department of Tropical Infectious Diseases, University of the Ryukyus, Okinawa 903-0213, Japan.
authors.forename: Takeshi
authors.initials: T
authors.lastname: Miyata
authors.forename: Tetsuya
authors.initials: T
authors.lastname: Harakuni
authors.forename: Hideki
authors.initials: H
authors.lastname: Sugawa
authors.forename: Jetsumon
authors.initials: J
authors.lastname: Sattabongkot
authors.forename: Aki
authors.initials: A
authors.lastname: Kato
authors.forename: Mayumi
authors.initials: M
authors.lastname: Tachibana
authors.forename: Motomi
authors.initials: M
authors.lastname: Torii
authors.forename: Takafumi
authors.initials: T
authors.lastname: Tsuboi
authors.forename: Takeshi
authors.initials: T
authors.lastname: Arakawa
mesh_terms: D000260:Adenoviruses, Human / Q000235:genetics*; D000818:Animals; D000913:Antibodies, Protozoan / Q000097:blood; D000953:Antigens, Protozoan / Q000235:genetics / Q000276:immunology*; D000954:Antigens, Surface / Q000235:genetics / Q000276:immunology*; D004195:Disease Models, Animal; D004337:Drug Carriers; D005260:Female; D005822:Genetic Vectors; D006801:Humans; D007074:Immunoglobulin G / Q000097:blood; D017780:Malaria Vaccines / Q000008:administration & dosage / Q000235:genetics / Q000276:immunology*; D016780:Malaria, Vivax / Q000517:prevention & control; D051379:Mice; D008807:Mice, Inbred BALB C; D013785:Thailand; D014611:Vaccination / Q000379:methods; D014614:Vaccines, Synthetic / Q000008:administration & dosage / Q000235:genetics / Q000276:immunology
chemical_list: D000913:Antibodies, Protozoan; D000953:Antigens, Protozoan; D000954:Antigens, Surface; D004337:Drug Carriers; D007074:Immunoglobulin G; D017780:Malaria Vaccines; C121473:Pvs25 protein, P vivax; D014614:Vaccines, Synthetic