Studies on a live type malaria vaccine. Molecular genetics of the parasite attenuation.

活型疟疾疫苗的研究。

• 批准号: 11307004
• 负责人: SUZUKI Mamoru
• 金额: $ 25.16万
• 依托单位: Gunma University
• 依托单位国家: 日本
• 项目类别: Grant-in-Aid for Scientific Research (A)
• 财政年份: 1999
• 资助国家: 日本
• 起止时间: 1999 至 2002
• 项目状态: 已结题
• 来源: https://kaken.nii.ac.jp/grant/KAKENHI-PROJECT-11307004/
• 关键词: live type malaria vaccine; attenuated parasites; two dementional electrophoresis; proteome analysis; NADH; Rag2-; -mice; cell transfer; immunological memory; マラリア; Plasmodium berghei; 弱毒化; プロテオソーム; 二次元電気泳動; 原虫; タンパク質; ワクチン; HGPRT; 遺伝子導入

Plasmodium berghei(NK65) is the most virulent parasite to mice causing 100% mortality by inoculating single live parasite. The XAT strain is a non-virulent mutant derived by a high X-ray irradiation on NK65 parasite. XAT does not induce severe malaria even by inoculating 107 parasites causing a self-limiting parasitemia in the mice. The survived mice show a long lasting immunity against challenge infection with the virulent NK65. (1) The parasite materials of NK65 and XAT were comparatively analyzed by 2-DE and 16 spots showed significant higher protein expressions in NK65 than those shown in XAT. Ten proteins were subjected to sequencing analyzes and in the non-virulence XAT, low level expression of the proteins functioning in NADH metabolic pathways were shown. (2) The immunological memory generated in mice after inoculation with XAT was studied by transferring spleen cells from the recovered mice to Rag2-/- mice in which both T and B lymphocytes are deficient. The results showed that the immunological memory persisted more than 120 days in the recovered mice. It looked that the T lymphocytes, in particular,played a key role in the immunological memory in this experimental model.

伯氏疟原虫（Plasmodiumberghei，NK 65）是一种对小鼠毒性最强的寄生虫，单次寄生可导致100%的小鼠死亡。XAT株是通过高X射线照射NK 65寄生虫而获得的无毒力突变株。XAT不会诱导严重的疟疾，即使是在小鼠中引起自限性寄生虫血症的107寄生虫。存活的小鼠对强毒NK 65的攻击感染表现出持久的免疫力。(1)对NK 65和XAT的虫体材料进行双向电泳分析，发现NK 65中有16个蛋白质点的表达量显著高于XAT。对10种蛋白质进行测序分析，并且在无毒XAT中，显示在NADH代谢途径中起作用的蛋白质的低水平表达。(2)通过将来自恢复小鼠的脾细胞转移到T和B淋巴细胞都缺乏的Rag 2-/-小鼠中，研究了接种XAT后小鼠中产生的免疫记忆。结果表明，恢复期小鼠的免疫记忆可持续120天以上。在本实验模型中，T淋巴细胞在免疫记忆中起着关键作用。

项目成果

鈴木 守: "11.日本におけるマラリア研究史-過去30年のあゆみ"日本における寄生虫学の研究. 6. 611-628 (1999)

铃木守：“11.日本疟疾研究史-过去30年的历史”日本寄生虫学研究6. 611-628（1999）。

Kawazu, S.: "Molecular characterization of a 2-Cys peroxiredoxin from the human malaria parasite Plasmodium falciparum"Molecular and Biochemical Parasitology. 116. 71-76 (2001)

Kawazu, S.：“来自人类疟疾寄生虫恶性疟原虫的 2-Cys 过氧化还原蛋白的分子特征”分子和生化寄生虫学。

Kawazu, S.: "Molecular characterization of a 2-Cys peroxiredoxin from the human malaria parasite Plasmodium falciparum"Mol. Biochem. Parasitol.. 116. 71-76 (2001)

Kawazu, S.：“来自人类疟原虫恶性疟原虫的 2-Cys 过氧化还原蛋白的分子特征”Mol。

Karasawa, M.: "Synthesis and structure of a peptide having partial sequence of Plasmodium farciparum enolase"Peptide Science 1999. 399-403 (2000)

Karasawa，M.：“具有鼠疟原虫烯醇酶部分序列的肽的合成和结构”肽科学1999.399-403(2000)

Sato, K.: "Application of yeast enolase as antigen for immunodiagnosis of malaria"Southeast Asian Journal of Tropical Medicine and Public Health. 31. 79-84 (2000)

Sato, K.：“酵母烯醇酶作为抗原在疟疾免疫诊断中的应用”《东南亚热带医学与公共卫生杂志》。