| Co-Investigator(Kenkyū-buntansha) |
ISHIBASHI Masahide OSAKA UNIVERSITY, KANNONJI INSTIUTE, DIRECTOR, 観音寺研究所, 所長(研究職) (70029776)
TAI Kumiko OSAKA UNIVERSITY, RESEARCH INTITUTE FOR MICROBIAL DISEASES, 教務職員 (00187907)
MITAMURA Toshihide OSAKA UNIVERSITY, RESEARCH INTITUTE FOR MICROBIAL DISEASES, ASSOCIATE PROFESSOR, 助教授 (80268846)
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| Research Abstract |
SE36 protein that we have purified before this study is a recombinant protein based on the N-terminal domain of P.falciparum SERA (Serine Repeat Antigen, 120kd). In the course of this study, the endotoxin-free SE36 protein purified under GMP condition has been supplied by Kannonji Institute of Research Foundation of Microbial Diseases of Osaka University. For clinical development of SE36 malaria vaccine, we have conducted the following experiments and obtained the promising results for pursuing the clinical trials of SE36 malaria vaccine. (1) Immunogenicity of SE36 protein was examined in three chimpanzees. SE36 was administered with aluminum hydroxide as adjuvant. In all animals, SE36 induced the specific antibodies with superior titers. All of the IgG subclasses were included in the induced IgG. (2) The duration of the antibody response was more than 1 year. After 2 years from the primary immunization, single booster administration of SE36 enhanced antibody induction at the highest l
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evel within two week. (3) To see the contribution of naturally acquired antibodies cross-reactive to SE36 in human to their anti-malarial immunity, we have conducted sero-epidemiological study in Solomon Islands where is falciparum malaria holo-endemic. We have measured antibody titers against SE36 protein and block 1-6 of MSP-1 (MSP-1_<1-6>) protein as well as blood parasitemia and malaria symptoms. Sero-positive rate for SE36 and MSP-1_<1-6> were 48% and 78% respectively. Most significantly, a strong negative correlation was found between antibody titer against SE36 and blood parasitemia as well as the symptoms. (4) The high titer serum were pooled and examined whether the sera inhibits the parasite cell proliferation or not in the culture. The inhibition of the cell proliferation of the high titer pooled serum was twice as much as that observed with low titer pooled serum. When high titer serum was pre-incubated with SE36 protein to neutralize the specific antibodies, the inhibition of the cell proliferation was cancelled more than 50%. The similar results were observed against three independent parasite strains that have three representative allelic types of SERA. These results demonstrate that N-terminal domain of SERA is one of the major target antigens for the protective malaria immunity Less
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