Sherwood J A, Copeland R S, Taylor K A, Abok K, Oloo A J, Were J B, Strickland G T, Gordon D M, Ballou W R, Bales J D, Wirtz R A, Wittes J, Gross M, Que J U, Cryz S J, Oster C N, Roberts C R, Sadoff J C
Clinical Research Centre, Nairobi, Kenya.
Vaccine. 1996 Jun;14(8):817-27. doi: 10.1016/0264-410x(95)00221-l.
It has been hypothesized that antibody induced by Plasmodium falciparum circumsporozoite protein vaccine would be effective against endemic human malaria. In a malaria endemic region of Kenya, 76 volunteers, in 38 pairs sleeping adjacently, were immunized with subunit circumsporozoite protein Asn-Ala-Asn-Pro tetrapeptide repeat-pseudomonas toxin A, or hepatitis B vaccine. After quinine and doxcycycline, volunteers were followed for illness daily, parasitemia weekly, antibody, T-lymphocyte responses, and treated if indicated. Anopheles mosquitoes resting in houses were collected, and tested for P. falciparum antigen, or dissected for sporozoites and tested for blood meal ABO type and P. falciparum antigen. Vaccine was safe, with side-effects similar in both groups, and immunogenic, engendering IgG antibody as high as 600 micrograms ml-1, but did not increase the proportion of volunteers with T-lymphocyte responses. Estimation of P. falciparum challenge averaged 0.194 potentially infective Anopheles bites/volunteer/ day. Mosquito blood meals showed no difference in biting intensity between vaccine and control groups. Both groups had similar malaria-free survival curves, cumulative positive blood slides, cumulative parasites mm-3, and numbers of parasites mm-3 on first positive blood slide, during three post-vaccination observation periods. Every volunteer had P. falciparum parastemia at least once. Vaccinees had 82% and controls 89% incidences of symptomatic parasitemia (P = 0.514, efficacy 9%, statistical power 95% probability of efficacy < 50%). Vaccine-induced anti-sporozoite antibody was not protective in this study. Within designed statistical precisions the present study is in agreement with efficacy studies in Colombia, Venezuela and Tanzania.
据推测，恶性疟原虫环子孢子蛋白疫苗诱导产生的抗体可有效对抗地方性人类疟疾。在肯尼亚一个疟疾流行地区，76名志愿者（38对相邻而眠）接种了亚单位环子孢子蛋白天冬酰胺-丙氨酸-天冬酰胺-脯氨酸四肽重复序列-铜绿假单胞菌毒素A，或乙型肝炎疫苗。在服用奎宁和强力霉素后，每天对志愿者的疾病情况进行跟踪，每周检测其寄生虫血症、抗体、T淋巴细胞反应，并在有指征时进行治疗。收集室内停歇的按蚊，检测恶性疟原虫抗原，或解剖检测子孢子，并检测其血餐的ABO血型和恶性疟原虫抗原。疫苗是安全的，两组的副作用相似，且具有免疫原性，可产生高达600微克/毫升的IgG抗体，但并未增加有T淋巴细胞反应的志愿者比例。对恶性疟原虫攻击的估计平均为每名志愿者每天0.194次可能具有感染性的按蚊叮咬。疫苗组和对照组的蚊虫血餐在叮咬强度上没有差异。在接种疫苗后的三个观察期内，两组的无疟疾生存曲线、累积阳性血涂片、累积寄生虫每立方毫米数量以及首次阳性血涂片上的寄生虫每立方毫米数量相似。每名志愿者至少有一次恶性疟原虫血症。接种疫苗者有症状的寄生虫血症发生率为82%，对照组为89%（P = 0.514，效力为9%，统计功效为效力<50%的概率为95%）。在本研究中，疫苗诱导的抗子孢子抗体没有保护作用。在设计的统计精度范围内，本研究与哥伦比亚、委内瑞拉和坦桑尼亚的效力研究结果一致。
