title: Evidences of protection against blood-stage infection of Plasmodium falciparum by the novel protein vaccine SE36.
abstract: An effective malaria vaccine is a public health priority. Proteins expressed during the blood-stage of the parasite life cycle have been proposed as good vaccine candidates. No such blood-stage vaccine, however, is available against Plasmodium falciparum, the deadliest Plasmodium species. We show here that P. falciparum serine repeat antigen 5 (SERA5) is a potential vaccine immunogen. We have constructed a new recombinant molecule of SERA5, namely SE36, based on previously reported SE47' molecule by removing the serine repeats. Epidemiological study in the holo-endemic population of Solomon Islands shows highly significant correlation of sero-conversion and malaria protective immunity against this antigen. Animal experiments using non-human primates, and a human phase 1a clinical trial assessed SE36 vaccine immunogenicity. Vaccination of squirrel monkeys with SE36 protein and aluminum hydroxyl gel (SE36/AHG) conferred protection against high parasitemia and boosted serum anti-SE36 IgG after P. falciparum parasite challenge. SE36/AHG was highly immunogenic in chimpanzees, where serum anti-SE36 IgG titers last more than one year. Phase 1a clinical trial (current controlled trials, ISRCTN78679862) demonstrated the safety and immunogenicity of SE36/AHG with 30 healthy adults and 10 placebo controls. Three subcutaneous administrations of 50 and 100microg dose of SE36/AHG were well-tolerated, with no severe adverse events; and resulted in 100% sero-conversion in both dose arms. The current research results for SE36/AHG provide initial clinical validation for future trials and suggest clues/strategies for further vaccine development.
authors.affiliation: Department of Molecular Protozoology, Research Institute for Microbial Diseases, Osaka University, Suita, Osaka, Japan. horii@biken.osaka-u.ac.jp
authors.forename: Toshihiro
authors.initials: T
authors.lastname: Horii
authors.forename: Hiroki
authors.initials: H
authors.lastname: Shirai
authors.forename: Li
authors.initials: L
authors.lastname: Jie
authors.forename: Ken J
authors.initials: KJ
authors.lastname: Ishii
authors.forename: Nirianne Q
authors.initials: NQ
authors.lastname: Palacpac
authors.forename: Takahiro
authors.initials: T
authors.lastname: Tougan
authors.forename: Mariko
authors.initials: M
authors.lastname: Hato
authors.forename: Nobuo
authors.initials: N
authors.lastname: Ohta
authors.forename: Albino
authors.initials: A
authors.lastname: Bobogare
authors.forename: Nana
authors.initials: N
authors.lastname: Arakaki
authors.forename: Yoshitsugu
authors.initials: Y
authors.lastname: Matsumoto
authors.forename: Junko
authors.initials: J
authors.lastname: Namazue
authors.forename: Toyokazu
authors.initials: T
authors.lastname: Ishikawa
authors.forename: Shigeharu
authors.initials: S
authors.lastname: Ueda
authors.forename: Michiaki
authors.initials: M
authors.lastname: Takahashi
mesh_terms: D000328:Adult; D000818:Animals; D000953:Antigens, Protozoan / Q000235:genetics / Q000276:immunology*; D004353:Drug Evaluation, Preclinical; D006801:Humans; D007074:Immunoglobulin G / Q000097:blood*; D017780:Malaria Vaccines / Q000008:administration & dosage / Q000235:genetics / Q000276:immunology*; D016778:Malaria, Falciparum / Q000453:epidemiology / Q000469:parasitology* / Q000517:prevention & control; D008542:Melanesia / Q000453:epidemiology; D018512:Parasitemia / Q000453:epidemiology / Q000469:parasitology / Q000517:prevention & control*; D010963:Plasmodium falciparum / Q000276:immunology; D011994:Recombinant Proteins / Q000235:genetics / Q000276:immunology; D012453:Saimiri; D016896:Treatment Outcome; D014611:Vaccination
chemical_list: D000953:Antigens, Protozoan; D007074:Immunoglobulin G; D017780:Malaria Vaccines; D011994:Recombinant Proteins; C480167:serine repeat antigen 5, Plasmodium falciparum