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

伯氏疟原虫(NK65)是对小鼠致死率最高的寄生虫，接种单一活体寄生虫可导致100%的死亡。XAT菌株是由NK65寄生虫经高强度X射线照射而产生的无毒突变株。XAT即使接种了107种寄生虫，也不会导致严重的疟疾，这会导致小鼠的自限性寄生虫血症。存活的小鼠对强毒NK65的攻击感染表现出持久的免疫力。(1)用双向凝胶电泳法对NK65和XAT的寄生材料进行了比较分析，发现NK65中有16个点的蛋白质表达显著高于XAT。对10个蛋白质进行了测序分析，在非毒力XAT中，NADH代谢途径中的蛋白质得到了低水平的表达。(2)通过将康复小鼠的脾细胞移植到T、B淋巴细胞均缺失的Rag2-/-小鼠身上，研究了XAT对小鼠免疫记忆的影响。结果表明，康复小鼠的免疫记忆持续时间在120天以上。看来，在这个实验模型中，T淋巴细胞在免疫记忆中扮演着关键角色。

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.