Department of Parasitology, Biomedical Primate Research Centre, Rijswijk, The Netherlands.
PLoS One. 2011;6(5):e20547. doi: 10.1371/journal.pone.0020547. Epub 2011 May 31.
Plasmodium falciparum apical membrane antigen 1 (PfAMA1) is a leading blood stage vaccine candidate. Plasmodium knowlesi AMA1 (PkAMA1) was produced and purified using similar methodology as for clinical grade PfAMA1 yielding a pure, conformational intact protein. Combined with the adjuvant CoVaccine HT™, PkAMA1 was found to be highly immunogenic in rabbits and the efficacy of the PkAMA1 was subsequently tested in a rhesus macaque blood-stage challenge model. Six rhesus monkeys were vaccinated with PkAMA1 and a control group of 6 were vaccinated with PfAMA1. A total of 50 µg AMA1 was administered intramuscularly three times at 4 week intervals. One of six rhesus monkeys vaccinated with PkAMA1 was able to control parasitaemia, upon blood stage challenge with P. knowlesi H-strain. Four out of the remaining five showed a delay in parasite onset that correlated with functional antibody titres. In the PfAMA1 vaccinated control group, five out of six animals had to be treated with antimalarials 8 days after challenge; one animal did not become patent during the challenge period. Following a rest period, animals were boosted and challenged again. Four of the six rhesus monkeys vaccinated with PkAMA1 were able to control the parasitaemia, one had a delayed onset of parasitaemia and one animal was not protected, while all control animals required treatment. To confirm that the control of parasitaemia was AMA1-related, animals were allowed to recover, boosted and re-challenged with P. knowlesi Nuri strain. All control animals had to be treated with antimalarials by day 8, while five out of six PkAMA1 vaccinated animals were able to control parasitaemia. This study shows that: i) Yeast-expressed PkAMA1 can protect against blood stage challenge; ii) Functional antibody levels as measured by GIA correlated inversely with the day of onset and iii) GIA IC(50) values correlated with estimated in vivo growth rates.
恶性疟原虫顶膜蛋白 1（PfAMA1）是一种主要的血阶段疫苗候选物。采用类似于临床级 PfAMA1 的生产和纯化方法生产和纯化了间日疟原虫 AMA1（PkAMA1），得到了一种纯净、构象完整的蛋白质。与佐剂 CoVaccine HT™ 联合使用，PkAMA1 在兔子中具有高度免疫原性，随后在恒河猴血阶段挑战模型中测试了 PkAMA1 的功效。6 只恒河猴接种了 PkAMA1，6 只对照组接种了 PfAMA1。总共肌肉内给予 50μg AMA1，每 4 周间隔 3 次。在间日疟原虫 H 株血阶段挑战时，有 1 只接种了 PkAMA1 的恒河猴能够控制寄生虫血症。其余 5 只中的 4 只表现出寄生虫发病延迟，这与功能抗体滴度相关。在 PfAMA1 接种的对照组中，在挑战后 8 天，有 5 只动物需要用抗疟药治疗；1 只动物在挑战期间未成为阳性。休息一段时间后，动物接受了加强免疫并再次接受了挑战。在接种了 PkAMA1 的 6 只恒河猴中，有 4 只能够控制寄生虫血症，1 只有寄生虫血症发病延迟，1 只动物未得到保护，而所有对照动物均需要治疗。为了确认寄生虫血症的控制与 AMA1 相关，动物被允许恢复，用间日疟原虫 Nuri 株加强免疫并再次挑战。所有对照动物在第 8 天均需要用抗疟药治疗，而接种了 PkAMA1 的 6 只动物中有 5 只能够控制寄生虫血症。本研究表明：i）酵母表达的 PkAMA1 可以预防血阶段挑战；ii）GIA 测量的功能抗体水平与发病日呈反比相关，iii）GIA IC（50）值与估计的体内生长率相关。
