Laboratory of Pathogen Infection and Immunity, Department of Public Health and Preventive Medicine; Wuxi School of Medicine, Jiangnan University, Wuxi, Jiangsu, China; Department of Anesthesiology, Affiliated Hospital of Jiangnan University, Wuxi, Jiangsu, China.
Laboratory of Pathogen Infection and Immunity, Department of Public Health and Preventive Medicine; Wuxi School of Medicine, Jiangnan University, Wuxi, Jiangsu, China.
Acta Trop. 2020 Oct;210:105591. doi: 10.1016/j.actatropica.2020.105591. Epub 2020 Jun 17.
Malaria is still an important challenge for global public health because of its extensive mortality and morbidity. Plasmodium ovale is mainly distributed in tropical regions of Africa and Asia. it includes two distinct ovale malaria species, which are P. ovale curtisi and P. ovale wallikeri. Apical membrane antigen-1 (AMA-1) is an asexual blood-stage protein which is essential for Plasmodium. Thus far, no study on gene polymorphism and immunogenicity of P. ovale AMA-1 (PoAMA-1) has been conducted. Amplified poama1 gene products from 14 P ovale curtisi samples and 12 P ovale wallikeri samples imported from Africa to Jiangsu Province, China were sequenced and their polymorphisms were analyzed. We expressed recombinant PoAMA-1 (rPoAMA-1, 53 kDa) proteins in an E. coli expression system and evaluated immune responses against the rPoAMA-1 in BALB/c mice. We identified a synonymous mutation in nucleotide position 333 of the pocama-1 gene and powama-1 did not reveal any variation. The humoral and cellular immune responses to rPoAMA-1 were evaluated using enzyme-linked immunosorbent assay (ELISA) and flow cytometry. rPoAMA-1-immunized mice produced specific antibodies as verified by immunoblotting. The rPoAMA-1 induced high antibody titers (1: 640,000), and had high avidity indexes (an average of 78.63% and 83.40%). The antibodies also recognized the native proteins, namely, crude antigen from blood stages. Cross-reactivity between rPocAMA-1 and rPowAMA-1 was observed. Moreover, rPoAMA-1 s induced interferon (IFN)-gamma-secreting cells in mice and increased lymphocyte proliferation response. Low genetic diversity was observed in poama-1 from the Jiangsu Province imported malaria cases, and further studies conclusively showed its strong immunogenicity. Significant cross-reactivity was found between rPocAMA-1 and rPowAMA-1, suggesting that a single PoAMA-1 antigen could be used to diagnose P. ovale curtisi or P. ovale wallikeri patient simultaneously. However, further evaluation needs to be carried out to validate the potential and limitations of PoAMA-1 as a candidate vaccine.
疟原虫仍然是全球公共卫生的一个重要挑战，因为它具有广泛的死亡率和发病率。卵形疟原虫主要分布在非洲和亚洲的热带地区。它包括两种不同的卵形疟原虫，即卵形疟原虫 curtisi 和卵形疟原虫 wallikeri。顶膜抗原-1（AMA-1）是一种无性血期蛋白，对疟原虫至关重要。迄今为止，还没有对卵形疟原虫 AMA-1（PoAMA-1）的基因多态性和免疫原性进行研究。从 14 株卵形疟原虫 curtisi 样本和 12 株卵形疟原虫 wallikeri 样本中扩增 poama1 基因产物，并对其进行测序和多态性分析。我们在大肠杆菌表达系统中表达了重组 PoAMA-1（rPoAMA-1，53kDa）蛋白，并在 BALB/c 小鼠中评估了针对 rPoAMA-1 的免疫反应。我们在核苷酸位置 333 发现了一个同义突变，而 powama-1 没有显示任何变化。使用酶联免疫吸附试验（ELISA）和流式细胞术评估 rPoAMA-1 的体液和细胞免疫反应。免疫印迹证实 rPoAMA-1 免疫小鼠产生了特异性抗体。rPoAMA-1 诱导高抗体滴度（1:640,000），具有高亲和力指数（平均为 78.63%和 83.40%）。这些抗体还识别了天然蛋白，即来自血期的粗抗原。观察到 rPocAMA-1 和 rPowAMA-1 之间的交叉反应。此外，rPoAMA-1 在小鼠中诱导干扰素（IFN）-γ分泌细胞，并增加淋巴细胞增殖反应。从江苏输入性疟疾病例中发现 poama-1 的遗传多样性较低，进一步的研究明确显示其具有很强的免疫原性。在 rPocAMA-1 和 rPowAMA-1 之间发现了显著的交叉反应，这表明单一的 PoAMA-1 抗原可用于同时诊断卵形疟原虫 curtisi 或卵形疟原虫 wallikeri 患者。然而，需要进一步评估以验证 PoAMA-1 作为候选疫苗的潜力和局限性。
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