Noland Gregory S, Hendel-Paterson Brett, Min Xinan M, Moormann Ann M, Vulule John M, Narum David L, Lanar David E, Kazura James W, John Chandy C
University of Minnesota, Minneapolis, MN 55455, USA.
Infect Immun. 2008 Dec;76(12):5721-8. doi: 10.1128/IAI.00591-08. Epub 2008 Sep 22.
In areas where levels of transmission of Plasmodium falciparum are high and stable, the age-related acquisition of high-level immunoglobulin G (IgG) antibodies to preerythrocytic circumsporozoite protein (CSP) and liver-stage antigen 1 (LSA-1) has been associated with protection from clinical malaria. In contrast, age-related protection from malaria develops slowly or not at all in residents of epidemic-prone areas with unstable low levels of malaria transmission. We hypothesized that this suboptimal clinical and parasitological immunity may in part be due to reduced antibodies to CSP or LSA-1 and/or vaccine candidate blood-stage antigens. Frequencies and levels of IgG antibodies to CSP, LSA-1, thrombospondin-related adhesive protein (TRAP), apical membrane antigen 1 (AMA-1), erythrocyte binding antigen 175 (EBA-175), and merozoite surface protein 1 (MSP-1) were compared in 243 Kenyans living in a highland area of unstable transmission and 210 residents of a nearby lowland area of stable transmission. Levels of antibodies to CSP, LSA-1, TRAP, and AMA-1 in the oldest age group (>40 years) in the unstable transmission area were lower than or similar to those of children 2 to 6 years old in the stable transmission area. Only 3.3% of individuals in the unstable transmission area had high levels of IgG (>2 arbitrary units) to both CSP and LSA-1, compared to 43.3% of individuals in the stable transmission area. In contrast, antibody levels to and frequencies of MSP-1 and EBA-175 were similar in adults in areas of stable and unstable malaria transmission. Suboptimal immunity to malaria in areas of unstable malaria transmission may relate in part to infrequent high-level antibodies to preerythrocytic antigens and AMA-1.
在恶性疟原虫传播水平高且稳定的地区，与年龄相关的针对前期环子孢子蛋白（CSP）和肝期抗原1（LSA-1）的高水平免疫球蛋白G（IgG）抗体的获得与预防临床疟疾有关。相比之下，在疟疾传播水平不稳定且较低的易流行地区的居民中，与年龄相关的疟疾防护发展缓慢或根本不发展。我们推测，这种次优的临床和寄生虫学免疫力可能部分归因于针对CSP或LSA-1以及/或候选疫苗血期抗原的抗体减少。比较了243名生活在传播不稳定的高原地区的肯尼亚人和210名附近传播稳定的低地地区居民中针对CSP、LSA-1、血小板反应蛋白相关黏附蛋白（TRAP）、顶膜抗原1（AMA-1）、红细胞结合抗原175（EBA-175）和裂殖子表面蛋白1（MSP-1）的IgG抗体的频率和水平。在传播不稳定地区最年长年龄组（>40岁）中，针对CSP、LSA-1、TRAP和AMA-1的抗体水平低于或类似于传播稳定地区2至6岁儿童的抗体水平。在传播不稳定地区，只有3.3%的个体针对CSP和LSA-1均具有高水平的IgG（>2个任意单位），而在传播稳定地区这一比例为43.3%。相比之下，在疟疾传播稳定和不稳定地区的成年人中，针对MSP-1和EBA-175的抗体水平及频率相似。疟疾传播不稳定地区对疟疾的次优免疫力可能部分与针对前期抗原和AMA-1的高水平抗体不常见有关。
