Inselburg J, Bathurst I C, Kansopon J, Barr P J, Rossan R
Department of Microbiology, Dartmouth Medical School, Hanover, New Hampshire 03755-3842.
Infect Immun. 1993 May;61(5):2048-52. doi: 10.1128/iai.61.5.2048-2052.1993.
We describe the third of three vaccination trials of Panamanian Aotus monkeys with a recombinant blood-stage antigen derived from the malaria parasite Plasmodium falciparum. Immunization was performed with an N-terminal region of the SERA antigen (serine repeat antigen protein), SERA 1, that contains a 262-amino-acid fragment including amino acids 24 to 285 of the 989-amino-acid SERA protein. Vaccinations were carried out with the recombinant protein mixed with either Freund's, MF75.2, or MF59.2 adjuvant. A control group that did not receive SERA 1 but only MF75.2 adjuvant was included. Monkeys vaccinated with the antigen MF59.2 mixture produced low anti-SERA 1 titers and were not protected. Monkeys vaccinated with antigen and Freund's adjuvant had, in general, a higher average anti-SERA 1 titer (107,278) than did monkeys immunized with SERA 1 and MF75.2 (40, 143), yet monkeys in both groups were well protected. Monkeys that received only MF75.2 developed neither detectable anti-SERA 1 nor anti-P. falciparum antibodies prior to or 10 days after parasite challenge, yet were apparently protected against infection. Monkeys vaccinated with either SERA 1 and Freund's, SERA 1 and MF75.2, or MF75.2 alone and that had been challenged but did not develop a countable parasitemia were treated with a curative dose of mefloquine 100 days after parasite challenge and then rechallenged 40 days later. None of the five rechallenged monkeys that had originally received SERA 1 and Freund's developed a countable parasitemia. Only one of five rechallenged monkeys that originally received SERA 1 and MF75.2 developed a high countable parasitemia, while two animals developed a barely countable parasitemia. Four of the rechallenged monkeys that had originally received only MF75.2 developed a moderate to high countable parasitemia. The results indicate that vaccination with SERA 1 and either Freund's or MF75.2 adjuvant provides protection and vaccination with MF75.2 alone can provide a temporary protection unrelated to the induction of anti-SERA 1 or antimalarial antibodies.
我们描述了对巴拿马夜猴进行的三项疟疾疫苗试验中的第三项,该试验使用了源自恶性疟原虫的重组血液期抗原。免疫接种采用SERA抗原(丝氨酸重复抗原蛋白)的N端区域SERA 1,它包含一个262个氨基酸的片段,涵盖了989个氨基酸的SERA蛋白中的第24至285位氨基酸。疫苗接种使用与弗氏佐剂、MF75.2或MF59.2佐剂混合的重组蛋白。设立了一个对照组,该组不接受SERA 1,只接受MF75.2佐剂。接种抗原与MF59.2混合物的猴子产生的抗SERA 1滴度较低,未得到保护。一般来说,接种抗原与弗氏佐剂的猴子的平均抗SERA 1滴度(107,278)高于接种SERA 1与MF75.2的猴子(40,143),但两组猴子均得到了良好的保护。只接受MF75.2的猴子在寄生虫攻击前或攻击后10天均未产生可检测到的抗SERA 1或抗恶性疟原虫抗体,但显然受到了感染保护。接种SERA 1与弗氏佐剂、SERA 1与MF75.2或单独MF75.2且受到攻击但未出现可计数寄生虫血症的猴子,在寄生虫攻击100天后接受了治疗剂量的甲氟喹治疗,然后在40天后再次受到攻击。最初接受SERA 1与弗氏佐剂的五只再次受到攻击的猴子中,没有一只出现可计数的寄生虫血症。最初接受SERA 1与MF75.2的五只再次受到攻击的猴子中,只有一只出现了高可计数的寄生虫血症,而两只动物出现了勉强可计数的寄生虫血症。最初只接受MF75.2的四只再次受到攻击的猴子出现了中度至高可计数的寄生虫血症。结果表明,接种SERA 1与弗氏佐剂或MF75.2佐剂可提供保护,单独接种MF75.2可提供与诱导抗SERA 1或抗疟抗体无关的临时保护。