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

伯氏疟原虫（Plasmodium berghei, NK65）是对小鼠毒性最大的寄生虫，接种单个活寄生虫可导致100%的死亡率。XAT菌株是由高x射线照射NK65寄生虫获得的无毒突变体。即使在小鼠体内接种107种寄生虫引起自限性寄生虫血症，XAT也不会诱发严重的疟疾。存活的小鼠对NK65病毒的攻击感染表现出持久的免疫力。(1)对NK65和XAT的寄主材料进行2-DE对比分析，发现NK65有16个位点的蛋白表达量显著高于XAT。对10个蛋白进行测序分析，在无毒性的XAT中，显示出在NADH代谢途径中起作用的蛋白的低水平表达。(2)通过将恢复后的小鼠脾脏细胞移植到T淋巴细胞和B淋巴细胞均缺乏的Rag2-/-小鼠体内，研究了XAT接种后小鼠产生的免疫记忆。结果表明，恢复后的小鼠免疫记忆持续120天以上。在这个实验模型中，T淋巴细胞尤其在免疫记忆中起着关键作用。

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.