高 IgG3 抗 ICB2-5 水平在没有出现症状的间日疟原虫感染个体中。

BACKGROUND

Plasmodium vivax has the potential to infect 2.85 billion individuals worldwide. Nevertheless, the limited number of studies investigating the immune status of individuals living in malaria-endemic areas, as well as the lack of reports investigating serological markers associated with clinical protection, has hampered development of vaccines for P. vivax. It was previously demonstrated that naturally total IgG against the N-terminus of P. vivax merozoite surface protein 1 (Pv-MSP1) was associated with reduced risk of malarial infection.

METHODS

Immune response against Pv-MSP1 (N-terminus) of 313 residents of the Rio Pardo rural settlement (Amazonas State, Brazil) was evaluated in a cross-sectional and longitudinal follow up over two months (on site) wherein gold standard diagnosis by thick blood smear and rRNA gene-based nested real-time PCR were used to discriminate symptomless Plasmodium vivax-infected individuals who did not develop clinical symptoms during a 2-months from those uninfected ones or who have had acute malaria. The acquisition of antibodies against Pv-MSP1 was also evaluated as survival analysis by prospective study over a year collecting information of new malaria infections in surveillance database.

RESULTS

The majority of P. vivax-infected individuals (52-67%) showed immune recognition of the N-terminus of Pv-MSP1. Interesting data on infected individuals who have not developed symptoms, total IgG levels against the N-terminus Pv-MSP1 were age-dependent and the IgG3 levels were significantly higher than levels of subjects had acute malaria or those uninfected ones. The total IgG anti ICB2-5 was detected to be an important factor of protection against new malaria vivax attacks in survival analysis in a prospective survey (p = 0.029).

CONCLUSIONS

The study findings illustrate the importance of IgG3 associated to 2-months of symptomless in P. vivax infected individuals and open perspectives for the rationale of malaria vaccine designs capable to sustain high levels of IgG3 against polymorphic malaria antigens.

背景

间日疟原虫有可能感染全球 28.5 亿人。然而，由于研究生活在疟疾流行地区的个体免疫状态的研究数量有限，以及缺乏与临床保护相关的血清学标志物的报告，阻碍了间日疟原虫疫苗的开发。先前已经证明，针对间日疟原虫裂殖子表面蛋白 1（Pv-MSP1）N 端的天然总 IgG 与降低疟疾感染风险有关。

方法

在为期两个月的（现场）横断面和纵向随访中，评估了 313 名里奥帕尔多农村居民（巴西亚马逊州）对 Pv-MSP1（N 端）的免疫反应，采用厚血涂片和 rRNA 基因巢式实时 PCR 金标准诊断来区分无症状间日疟原虫感染个体，这些个体在两个月内没有出现临床症状，而没有感染的个体或患有急性疟疾的个体。通过前瞻性研究，在一年时间内收集监测数据库中的新疟疾感染信息，对抗体对 Pv-MSP1 的获得情况进行生存分析。

结果

大多数间日疟原虫感染个体（52-67%）表现出对 Pv-MSP1 N 端的免疫识别。有趣的数据是，无症状感染个体中，针对 Pv-MSP1 N 端的总 IgG 水平随年龄增长而变化，IgG3 水平明显高于急性疟疾或未感染个体。在生存分析中，前瞻性调查发现，总 IgG 抗 ICB2-5 是预防新的间日疟原虫攻击的一个重要因素（p=0.029）。