Malaria Vaccine Development Branch, National Institute of Allergy and Infectious Diseases, National Institutes of Health, Rockville, MD 20852, USA.
Vaccine. 2011 Mar 9;29(12):2255-61. doi: 10.1016/j.vaccine.2011.01.043. Epub 2011 Jan 31.
Clinical development of malaria vaccines progresses from trials in malaria naïve adults to malaria exposed adults followed by malaria exposed children. It is not well known whether immune responses in non-target populations are predictive of those in target populations, particularly in African children. Therefore humoral responses in three different populations (U.S. adults, Malian adults and Malian children) were compared in this study. They were immunized with 80 μg of Apical Membrane Antigen 1 (AMA1)/alhydrogel on days 0 and 28. Sera were collected on days 0 and 42; antibody levels were determined by ELISA and the functionality of antibodies was evaluated by Growth Inhibition Assay. After immunization, there was no significant difference in antibody levels between the Malian children and the Malian adults, but U.S. adults showed lower antibody levels. Vaccination did not significantly change growth-inhibitory activity in Malian adults, but inhibition increased significantly in both U.S. adults and Malian children. Vaccine-induced inhibitory activity was reversed by pre-incubation with AMA1 protein, but pre-existing infection-induced inhibition was not. This study shows that humoral responses elicited by the AMA1 vaccine varied depending on the population, most likely reflecting different levels of previous malaria exposure. Thus predicting immune responses from non-target populations is not desirable.
疟疾疫苗的临床开发从在无疟疾的成年人中进行试验开始,然后在疟疾暴露的成年人中进行,最后在疟疾暴露的儿童中进行。目前尚不清楚非目标人群的免疫反应是否可预测目标人群的免疫反应,尤其是在非洲儿童中。因此,本研究比较了三个不同人群(美国成年人、马里成年人和马里儿童)的体液反应。他们在第 0 天和第 28 天接受 80 μg 的顶膜抗原 1(AMA1)/氢氧化铝凝胶免疫。在第 0 天和第 42 天收集血清;通过 ELISA 测定抗体水平,并通过生长抑制试验评估抗体的功能。免疫后,马里儿童和马里成年人之间的抗体水平没有显著差异,但美国成年人的抗体水平较低。疫苗接种并没有显著改变马里成年人的生长抑制活性,但美国成年人和马里儿童的抑制作用都显著增加。疫苗诱导的抑制活性可通过与 AMA1 蛋白预孵育而逆转,但先前感染诱导的抑制则不能。本研究表明,AMA1 疫苗引起的体液反应因人群而异,这很可能反映了不同程度的先前疟疾暴露。因此,从非目标人群预测免疫反应是不可取的。