Lusingu John P A, Jensen Anja T R, Vestergaard Lasse S, Minja Daniel T, Dalgaard Michael B, Gesase Samwel, Mmbando Bruno P, Kitua Andrew Y, Lemnge Martha M, Cavanagh David, Hviid Lars, Theander Thor G
Centre for Medical Parasitology, Institute for Medical Microbiology and Immunology, University of Copenhagen, Denmark.
Infect Immun. 2006 May;74(5):2867-75. doi: 10.1128/IAI.74.5.2867-2875.2006.
Antibodies to variant surface antigen have been implicated as mediators of malaria immunity in studies measuring immunoglobulin G (IgG) binding to infected erythrocytes. Plasmodium falciparum erythrocyte membrane protein 1 (PfEMP1) is an important target for these antibodies, but no study has directly linked the presence of PfEMP1 antibodies in children to protection. We measured plasma IgG levels to the cysteine-rich interdomain region 1alpha (CIDR1alpha) of VAR4 (VAR4-CIDR1alpha), a member of a semiconserved PfEMP1 subfamily, by enzyme-linked immunosorbent assay in 561 Tanzanian individuals, who were monitored clinically for 7 months. The participants resided in Mkokola (a high-transmission village where malaria is holoendemic) or Kwamasimba (a moderate-transmission village). For comparison, plasma IgG levels to two merozoite surface protein 1 (MSP1) constructs, MSP1-19 and MSP1 block 2, and a control CIDR1 domain were measured. VAR4-CIDR1alpha antibodies were acquired at an earlier age in Mkokola than in Kwamasimba, but after the age of 10 years the levels were comparable in the two villages. After controlling for age and other covariates, the risk of having anemia at enrollment was reduced in VAR4-CIDR1alpha responders for Mkokola (adjusted odds ratio [AOR], 0.49; 95% confidence interval [CI], 0.29 to 0.88; P = 0.016) and Kwamasimba (AOR, 0.33; 95% CI, 0.16 to 0.68; P = 0.003) villages. The risk of developing malaria fever was reduced among individuals with a measurable VAR4-CIDR1alpha response from Mkokola village (AOR, 0.51; 95% CI, 0.29 to 0.89; P = 0.018) but not in Kwamasimba. Antibody levels to the MSP1 constructs and the control CIDR1alpha domain were not associated with morbidity protection. These data strengthen the concept of developing vaccines based on PfEMP1.
在测量免疫球蛋白G（IgG）与受感染红细胞结合的研究中，针对变异表面抗原的抗体被认为是疟疾免疫的介质。恶性疟原虫红细胞膜蛋白1（PfEMP1）是这些抗体的重要靶点，但尚无研究直接将儿童体内PfEMP1抗体的存在与保护作用联系起来。我们通过酶联免疫吸附测定法，检测了561名坦桑尼亚人的血浆中针对半保守PfEMP1亚家族成员VAR4的富含半胱氨酸的结构域间区域1α（CIDR1α）（VAR4-CIDR1α）的IgG水平，并对他们进行了7个月的临床监测。参与者居住在姆科科拉（一个疟疾高度流行的高传播村庄）或夸马辛巴（一个中度传播村庄）。作为对照，检测了血浆中针对两种裂殖子表面蛋白1（MSP1）构建体MSP1-19和MSP1阻断区2以及一个对照CIDR1结构域的IgG水平。在姆科科拉，针对VAR4-CIDR1α的抗体在比夸马辛巴更小的年龄获得，但在10岁以后，两个村庄的抗体水平相当。在控制年龄和其他协变量后，姆科科拉（调整优势比[AOR]，0.49；95%置信区间[CI]，0.29至0.88；P = 0.016）和夸马辛巴（AOR，0.33；95%CI，0.16至0.68；P = 0.003）村庄中，对VAR4-CIDR1α有反应者在入组时患贫血的风险降低。在姆科科拉村有可测量的VAR4-CIDR1α反应的个体中，患疟疾发热的风险降低（AOR，0.51；95%CI，0.29至0.89；P = 0.018），但在夸马辛巴村没有降低。针对MSP1构建体和对照CIDR1α结构域的抗体水平与发病保护无关。这些数据强化了基于PfEMP1开发疫苗的概念。
