1. Evidences of protection against blood-stage infection of Plasmodium falciparum by the novel protein vaccine SE36.
- Author
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Horii T, Shirai H, Jie L, Ishii KJ, Palacpac NQ, Tougan T, Hato M, Ohta N, Bobogare A, Arakaki N, Matsumoto Y, Namazue J, Ishikawa T, Ueda S, and Takahashi M
- Subjects
- Adult, Animals, Antigens, Protozoan genetics, Drug Evaluation, Preclinical, Humans, Malaria Vaccines administration & dosage, Malaria Vaccines genetics, Malaria, Falciparum epidemiology, Malaria, Falciparum prevention & control, Melanesia epidemiology, Parasitemia epidemiology, Parasitemia parasitology, Plasmodium falciparum immunology, Recombinant Proteins genetics, Recombinant Proteins immunology, Saimiri, Treatment Outcome, Vaccination, Antigens, Protozoan immunology, Immunoglobulin G blood, Malaria Vaccines immunology, Malaria, Falciparum parasitology, Parasitemia prevention & control
- 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.
- Published
- 2010
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