健康的无疟疾史成年人中对单一等位基因 PfAMA1 疫苗的体液免疫反应。
Humoral immune responses to a single allele PfAMA1 vaccine in healthy malaria-naïve adults.
机构信息
Biomedical Primate Research Centre, Rijswijk, The Netherlands.
出版信息
PLoS One. 2012;7(6):e38898. doi: 10.1371/journal.pone.0038898. Epub 2012 Jun 29.
UNLABELLED
Plasmodium falciparum: apical membrane antigen 1 (AMA1) is a candidate malaria vaccine antigen expressed on merozoites and sporozoites. The polymorphic nature of AMA1 may compromise vaccine induced protection. The humoral response induced by two dosages (10 and 50 µg) of a single allele AMA1 antigen (FVO) formulated with Alhydrogel, Montanide ISA 720 or AS02 was investigated in 47 malaria-naïve adult volunteers. Volunteers were vaccinated 3 times at 4 weekly intervals and serum samples obtained four weeks after the third immunization were analysed for (i) Antibody responses to various allelic variants, (ii) Domain specificity, (iii) Avidity, (iv) IgG subclass levels, by ELISA and (v) functionality of antibody responses by Growth Inhibition Assay (GIA). About half of the antibodies induced by vaccination cross reacted with heterologous AMA1 alleles. The choice of adjuvant determined the magnitude of the antibody response, but had only a marginal influence on specificity, avidity, domain recognition or subclass responses. The highest antibody responses were observed for AMA1 formulated with AS02. The Growth Inhibition Assay activity of the antibodies was proportional to the amount of antigen specific IgG and the functional capacity of the antibodies was similar for heterologous AMA1-expressing laboratory strains.
TRIAL REGISTRATION
ClinicalTrials.gov NCT00730782.
未加标签
恶性疟原虫:顶膜抗原 1(AMA1)是一种在裂殖子和子孢子上表达的候选疟疾疫苗抗原。AMA1 的多态性可能会影响疫苗诱导的保护作用。用 Alhydrogel、Montanide ISA 720 或 AS02 配制的单一等位基因 AMA1 抗原(FVO)的两种剂量(10 和 50 µg)在 47 名疟原虫初免的成年志愿者中诱导的体液反应进行了研究。志愿者每 4 周接种 3 次,在第 3 次免疫后 4 周采集血清样本,通过 ELISA 分析(i)针对各种等位基因变异的抗体反应,(ii)结构域特异性,(iii)亲和力,(iv)IgG 亚类水平,(v)通过生长抑制测定(GIA)分析抗体反应的功能。接种疫苗诱导的抗体约有一半与异源 AMA1 等位基因发生交叉反应。佐剂的选择决定了抗体反应的强度,但对特异性、亲和力、结构域识别或亚类反应的影响只有很小的影响。用 AS02 配制的 AMA1 产生的抗体反应最高。抗体的生长抑制测定活性与抗原特异性 IgG 的量成正比,并且针对异源表达 AMA1 的实验室株,抗体的功能能力相似。
试验注册
ClinicalTrials.gov NCT00730782。