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应用反向疫苗学方法研究疟原虫属跨膜碳酸酐酶作为疟疾预防疫苗候选物。

A reverse vaccinology approach on transmembrane carbonic anhydrases from Plasmodium species as vaccine candidates for malaria prevention.

机构信息

Department of Energy and Environmental Biotechnology, National Institute of Genetic Engineering and Biotechnology (NIGEB), 14965/161, Tehran, Iran.

Faculty of Medicine and Health Technology, Tampere University, Tampere, Finland.

出版信息

Malar J. 2022 Jun 15;21(1):189. doi: 10.1186/s12936-022-04186-7.

DOI:10.1186/s12936-022-04186-7
PMID:35706028
原文链接:https://pmc.ncbi.nlm.nih.gov/articles/PMC9199335/
Abstract

BACKGROUND

Malaria is a significant parasitic infection, and human infection is mediated by mosquito (Anopheles) biting and subsequent transmission of protozoa (Plasmodium) to the blood. Carbonic anhydrases (CAs) are known to be highly expressed in the midgut and ectoperitrophic space of Anopheles gambiae. Transmembrane CAs (tmCAs) in Plasmodium may be potential vaccine candidates for the control and prevention of malaria.

METHODS

In this study, two groups of transmembrane CAs, including α-CAs and one group of η-CAs were analysed by immunoinformatics and computational biology methods, such as predictions on transmembrane localization of CAs from Plasmodium spp., affinity and stability of different HLA classes, antigenicity of tmCA peptides, epitope and proteasomal cleavage of Plasmodium tmCAs, accessibility of Plasmodium tmCAs MHC-ligands, allergenicity of Plasmodium tmCAs, disulfide-bond of Plasmodium tmCAs, B cell epitopes of Plasmodium tmCAs, and Cell type-specific expression of Plasmodium CAs.

RESULTS

Two groups of α-CAs and one group of η-CAs in Plasmodium spp. were identified to contain tmCA sequences, having high affinity towards MHCs, high stability, and strong antigenicity. All putative tmCAs were predicted to contain sequences for proteasomal cleavage in antigen presenting cells (APCs).

CONCLUSIONS

The predicted results revealed that tmCAs from Plasmodium spp. can be potential targets for vaccination against malaria.

摘要

背景

疟疾是一种重要的寄生虫感染，人类感染是由蚊子（按蚊）叮咬和随后原生动物（疟原虫）传播到血液中引起的。已知碳酸酐酶（CA）在按蚊的中肠和外质空间中高度表达。疟原虫中的跨膜 CA（tmCA）可能是控制和预防疟疾的潜在疫苗候选物。

方法

在这项研究中，两组跨膜 CA，包括α-CA 和一组 η-CA，通过免疫信息学和计算生物学方法进行了分析，例如预测疟原虫 spp. 中的 CA 跨膜定位、不同 HLA 类别的亲和力和稳定性、tmCA 肽的抗原性、疟原虫 tmCA 的表位和蛋白酶体切割、疟原虫 tmCA 的 MHC 配体可及性、疟原虫 tmCA 的变应原性、疟原虫 tmCA 的二硫键、疟原虫 tmCA 的 B 细胞表位以及疟原虫 CA 的细胞类型特异性表达。

结果

在疟原虫 spp. 中鉴定出两组 α-CA 和一组 η-CA 包含 tmCA 序列，具有与 MHC 高亲和力、高稳定性和强抗原性。所有推定的 tmCA 都被预测在抗原呈递细胞（APC）中含有蛋白酶体切割序列。

结论

预测结果表明，疟原虫的 tmCA 可以作为疟疾疫苗接种的潜在靶点。

https://cdn.ncbi.nlm.nih.gov/pmc/blobs/b28d/9202210/497aa6505dd0/12936_2022_4186_Fig2_HTML.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/b28d/9202210/c9a55b29b40c/12936_2022_4186_Fig1_HTML.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/b28d/9202210/497aa6505dd0/12936_2022_4186_Fig2_HTML.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/b28d/9202210/c9a55b29b40c/12936_2022_4186_Fig1_HTML.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/b28d/9202210/497aa6505dd0/12936_2022_4186_Fig2_HTML.jpg

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