研究仍在继续:探索设计有效的多表位疟疾候选疫苗的免疫信息学平台。

Biotechnologia Pub Date : 2025-06-30 eCollection Date: 2025-01-01 DOI:10.5114/bta/204528
Charles Osuji, Godwin Etuk-Udo
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引用次数: 0

摘要

背景:尽管有预防和控制措施,但疟疾造成的普遍公共健康威胁,特别是在发展中国家,仍然是一个令人严重关切的问题。虽然疫苗接种是防治疟疾的一种有力手段,但由于在RTS,S疫苗推出之前的多次尝试都不成功,疫苗接种并未得到充分利用。考虑到寄生虫生命周期的复杂性,疟疾疫苗开发的一个主要挑战仍然是确定能够产生强大免疫力的有效靶点。利用新批准的疟疾疫苗取得的突破,以新的决心继续努力制定更有效的预防解决办法。材料和方法:本研究采用标准结构生物信息学管道设计了一种针对疟原虫,特别是恶性疟原虫的多表位亚单位疫苗。根据与疫苗的相似性,从恶性疟原虫不同生命周期阶段表达的蛋白的变异表面抗原中提取了30个亚基表位。这些表位与合适的佐剂和连接物结合成疫苗结构,然后进行严格的下游分析。结果:从最初的133个表位中,选择了30个适合疫苗的表位,最终得到了包含570个氨基酸残基的疫苗结构。其中包括12个线性b细胞,11个细胞毒性t淋巴细胞和7个辅助t淋巴细胞表位,所有表位都具有良好的预测结构,抗原和物理化学性质。该构建还显示出强大的全球人口覆盖率(95.04%),强大的分子结合和模拟免疫应答。结论:随着“组学”技术通过反向疫苗学的发展,发现和设计有希望的候选疫苗变得更加容易,而无需许多具有挑战性的严格实验。这项研究强调了免疫信息学辅助方法在加速有效疟疾疫苗开发方面的潜力。
本文章由计算机程序翻译,如有差异,请以英文原文为准。
Search continues: Exploring immunoinformatics platforms for designing an effective multiepitope malaria vaccine candidate.

Background: The prevailing public health threat posed by malaria, especially in developing countries, remains a serious concern despite the availability of preventive and control measures. While vaccination offers a powerful means of combating malaria, it has not been fully exploited due to previous unsuccessful attempts before the launch of the RTS,S vaccine. A major challenge in malaria vaccine development continues to be the identification of effective targets capable of eliciting robust immunity, given the complexity of the parasites' life cycle. Leveraging on the breakthrough of the newly approved malaria vaccine, efforts to develop more effective prophylactic solutions continue with renewed determination.

Materials and methods: In this study, a standard structural bioinformatics pipeline was employed to design a multiepitope subunit vaccine against Plasmodium, particularly P. falciparum. Thirty subunit epitopes were mined from selected variant surface antigens of P. falciparum proteins expressed at different stages of its life cycle, based on their vaccine-likeness. These epitopes were conjugated with suitable adjuvants and linkers into a vaccine construct, which was then subjected to stringent downstream analyses.

Results: Out of an initial pool of 133 epitopes, 30 vaccine-fit epitopes were selected, resulting in a final vaccine construct comprising 570 amino acid residues. This included 12 linear B-cells, 11 cytotoxic T-lymphocytes, and 7 helper T-lymphocyte epitopes, all with favorable predicted structural, antigenic, and physicochemical properties. The construct also demonstrated strong global population coverage (95.04%), robust molecular binding, and simulated immune responses.

Conclusions: With the evolving "Omics" technologies through reverse vaccinology, discovering and designing promising vaccine candidates becomes easier without many challenging experimental rigors. This study highlights the potential of immunoinformatics-aided approaches in accelerating effective malaria vaccine development.

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