Details

Autor(en) / Beteiligte

• Horii, Toshihiro
• Shirai, Hiroki
• Jie, Li
• Ishii, Ken J
• Palacpac, Nirianne Q
• Tougan, Takahiro
• Hato, Mariko
• Ohta, Nobuo
• Bobogare, Albino
• Arakaki, Nana
• Matsumoto, Yoshitsugu
• Namazue, Junko
• Ishikawa, Toyokazu
• Ueda, Shigeharu
• Takahashi, Michiaki

Titel

Evidences of protection against blood-stage infection of Plasmodium falciparum by the novel protein vaccine SE36

Ist Teil von

• Parasitology international, 2010-09, Vol.59 (3), p.380-386

Ort / Verlag

Netherlands: Elsevier Ireland Ltd

Erscheinungsjahr

2010

Quelle

MEDLINE

Beschreibungen/Notizen

• 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 100 μg 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.