Efficacy of vaccines containing rhoptry-associated proteins RAP1 and RAP2 of Plasmodium falciparum in Saimiri boliviensis monkeys
Efficacy of vaccines containing rhoptry-associated proteins RAP1 and RAP2 of Plasmodium falciparum in Saimiri boliviensis monkeys
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DOI：
10.4269/ajtmh.2000.62.466
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发表时间：
2000-04-01
影响因子：
3.3
通讯作者：
Saul, A
中科院分区：
文献类型：
--
作者：
Collins, WE;Walduck, A;Saul, A
在玻利维亚赛米尔猴中使用恶性疟原虫的棒状体相关蛋白 1 和 2（RAP1 和 RAP2）进行了疫苗试验，以比较寄生虫来源的蛋白（PfRAP1 和 2）和重组蛋白（rRAP1 和 2）诱导保护性免疫反应的能力，并寻找适合人类使用的佐剂。八组每组 6 只猴子用寄生虫衍生的或重组 RAP1 和 2 组用弗氏完全佐剂 (FCA) 免疫，然后用弗氏不完全佐剂 (FIA)、Montanide ISA720 佐剂或 CRL1005 佐剂免疫。重组 RAP1 和 RAP2 也与 Montanide ISA720 一起单独施用。 3次免疫后，猴子接受静脉注射50,000只恶性疟原虫乌干达帕莱阿尔托株寄生虫的攻击。在使用 FCA/FIA 疫苗接种的动物中，6 只对照猴中的 1 只、用 PfRAP1 和 2 免疫的 6 只猴子中的 3 只、用 rRAP1 和 2 免疫的 6 只猴子中的 2 只不需要药物治疗。在接种 Montanide ISA720 佐剂的猴子中，6只对照猴中的 0 只、用 RAP1 免疫的 6 只猴子中的 2 只、用 rRAP1 免疫的 6 只猴子中的 1 只、用 RAP2 免疫的 6 只猴子中的 4 只不需要药物治疗。 6 只用 PfRAP1 免疫的猴子和 2 只用 CRL1005 免疫的猴子中的 2 只不需要治疗。所有接受 RAP1、RAP2 或两者的组的初始寄生虫增殖率均显着下降，并且抗 RAP2 抗体与增殖率之间存在显着负相关。第一次攻击后 126 天，动物再次受到同源寄生虫攻击。第一次攻击后不需要药物治疗的猴子在再次攻击后没有出现可检测到的寄生虫血症。
A vaccine trial was conducted with rhoptry-associated proteins 1 and 2 (RAP1 and RAP2) of Plasmodium falciparum in Saimiri boliviensis monkeys to compare the ability of parasite-derived (PfRAP1 and 2) and recombinant proteins (rRAP1 and 2) to induce protective immune responses and to find adjuvants suitable for use in humans. Eight groups of 6 monkeys each were immunized with parasite-derived or recombinant RAP1 and 2 with Freund's complete adjuvant (FCA) followed by Freund's incomplete adjuvant (FIA), Montanide ISA720 adjuvant, or CRL1005 adjuvant. Recombinant RAP1 and RAP2 were also administered separately, with Montanide ISA720. After 3 immunizations, monkeys were challenged by iv inoculation of 50,000 parasites of the Uganda Pale Alto strain of P. falciparum. Of the animals vaccinated using FCA/FIA, I of 6 control monkeys, 3 of 6 immunized with PfRAP1 and 2, and 2 of 6 with rRAP1 and 2 did not require drug treatment. Of the monkeys vaccinated with Montanide ISA720 adjuvant, 0 of the 6 control monkeys, 2 of 6 immunized with RAP1 and 2, 1 of 6 immunized with rRAP1, and 4 of 6 immunized with RAP2 did not require drug treatment. Two of 6 monkeys immunized with PfRAP1 and 2 with CRL1005 did not require treatment. All groups receiving RAP1, RAP2, or both had a significant decrease in initial parasite multiplication rates and there was a significant negative correlation between anti-RAP2 antibody and multiplication rates. Animals were rechallenged with the homologous parasite 126 days after the first challenge. Of the monkeys that did not require drug treatment after the first challenge, none developed detectable parasitemia following rechallenge.