Laboratório de Pesquisa em Apicomplexa, Instituto Carlos Chagas, Fundação Oswaldo Cruz (Fiocruz), Curitiba, PR, Brazil.
Grupo de Imunologia Celular e Molecular, Instituto Carlos Chagas, Fundação Oswaldo Cruz (Fiocruz), Curitiba, PR, Brazil.
Front Immunol. 2024 Oct 10;15:1455454. doi: 10.3389/fimmu.2024.1455454. eCollection 2024.
Malaria represents a challenging global public health task, with being the predominant parasite in Brazil and the most widely distributed species throughout the world. Developing a vaccine against malaria demands innovative strategies, and targeting gametocyte antigens shows promise for blocking transmission prevention. Among these antigens, Pvs47, expressed in gametocytes, has shown remarkable efficacy in transmission blocking. However, remains underexplored in vaccine formulations. This study employed methods to comprehensively characterize the physicochemical properties, structural attributes, epitope presence, and conservation profile of Pvs47. Additionally, we assessed its antigenicity in individuals exposed to malaria in endemic Brazilian regions. Recombinant protein expression occurred in a eukaryotic system, and antigenicity was evaluated using immunoenzymatic assays. The responses of naturally acquired IgM, total IgG, and IgG subclasses were analyzed in three groups of samples from Amazon region. Notably, all samples exhibited anti-Pvs47 IgM and IgG antibodies, with IgG3 predominating. Asymptomatic patients demonstrated stronger IgG responses and more diverse subclass responses. Anti-Pvs47 IgM and IgG responses in symptomatic individuals decrease over time. Furthermore, we observed a negative correlation between anti-Pvs47 IgM response and gametocytemia in samples of symptomatic patients, indicating a gametocyte-specific response. Additionally, negative correlation was observed among anti-Pvs47 antibody response and hematocrit levels. Furthermore, comparative analysis with widely characterized blood antigens, PvAMA1 and PvMSP1, revealed that Pvs47 was equally or more recognized than both proteins. In addition, there is positive correlation between blood asexual and sexual stage immune responses. In summary, our study unveils a significant prevalence of anti-Pvs47 antibodies in diverse Amazonian samples and the importance of IgM response for gametocytes depuration. These findings regarding the characterization and antigenicity of Pvs47 provide crucial insights for potential integration into vaccine formulations.
疟疾是一项具有挑战性的全球公共卫生任务, 在巴西主要寄生虫为 ,也是世界上分布最广的物种。开发针对 疟疾的疫苗需要创新的策略,针对配子体抗原显示出阻断传播预防的前景。在这些抗原中,在配子体中表达的 Pvs47 在阻断传播方面显示出显著的效果。然而,在疫苗配方中仍未得到充分探索。本研究采用多种方法全面描述了 Pvs47 的理化性质、结构属性、表位存在和保守性特征。此外,我们评估了它在暴露于巴西流行地区疟疾的个体中的抗原性。重组蛋白在真核系统中表达,并使用免疫酶测定法评估其抗原性。分析了来自亚马逊地区的三组样本中天然获得的 IgM、总 IgG 和 IgG 亚类的反应。值得注意的是,所有样本均表现出抗 Pvs47 IgM 和 IgG 抗体,其中 IgG3 占主导地位。无症状患者表现出更强的 IgG 反应和更多样化的亚类反应。有症状个体的抗 Pvs47 IgM 和 IgG 反应随时间推移而下降。此外,我们观察到有症状患者样本中抗 Pvs47 IgM 反应与配子体血症之间呈负相关,表明存在配子体特异性反应。此外,抗 Pvs47 抗体反应与血细胞比容水平之间也存在负相关。此外,与广泛表征的血液抗原 PvAMA1 和 PvMSP1 进行比较分析表明,Pvs47 与这两种蛋白的识别率相当或更高。此外,血液无性和有性阶段免疫反应之间存在正相关。总之,我们的研究揭示了在不同的亚马逊样本中存在大量的抗 Pvs47 抗体,以及 IgM 反应对配子体清除的重要性。这些关于 Pvs47 的特性和抗原性的发现为潜在的疫苗配方整合提供了重要的见解。