将 PSOP26 鉴定为一种配子体表抗原，与 PSOP25 融合后可提高传播阻断活性。

Characterization of PSOP26 as an ookinete surface antigen with improved transmission-blocking activity when fused with PSOP25.

机构信息

Department of Immunology, College of Basic Medical Sciences, China Medical University, Shenyang, 110122, Liaoning, China.

Department of Laboratory Medicine, Shengjing Hospital of China Medical University, Shenyang, 110004, China.

出版信息

Parasit Vectors. 2022 May 23;15(1):175. doi: 10.1186/s13071-022-05294-8.

DOI:10.1186/s13071-022-05294-8

PMID:35606790

原文链接:https://pmc.ncbi.nlm.nih.gov/articles/PMC9125894/

Abstract

BACKGROUND

The Plasmodium zygote-to-ookinete developmental transition is an essential step for establishing an infection in the mosquito vector, and antigens expressed during this stage are potential targets for transmission-blocking vaccines (TBVs). The secreted ookinete protein 26 (PSOP26) is a newly identified ookinete surface protein. The anti-PSOP26 serum has moderate transmission-blocking activity, indicating the benefit of further investigating this protein as a target for TBVs.

METHODS

The function of psop26 was analyzed by targeted gene disruption. A chimeric PSOP25-PSOP26 protein was expressed in the Escherichia coli system. The PSOP25-PSOP26 fusion protein, along with mixed (PSOP25 + PSOP26) or single proteins (PSOP26 or PSOP25), were used for the immunization of mice. The antibody titers and immunogenicity of individual sera were analyzed by enzyme-linked immunoassay (ELISA), indirect immunofluorescence assay (IFA), and Western blot. The transmission-blocking activity of sera from different immunization schemes was assessed using in vitro and in vivo assays.

RESULTS

PSOP26 is a surface protein expressed in Plasmodium gametes and ookinetes. The protein is dispensable for asexual blood-stage development, gametogenesis, and zygote formation, but is essential for the zygote-to-ookinete developmental transition. Specifically, both the prevalence of infections and oocyst densities were decreased in mosquitoes fed on psop26-null mutants. Mixtures of individual PSOP25 and PSOP26 fragments (PSOP25 + PSOP26), as well as chimeras (PSOP25-PSOP26), elicited high antibody levels in mice, with no immunological interference. Antisera against the mixed and fusion proteins elicited higher transmission-reducing activity (TRA) than antisera against the single PSOP26 antigen, but comparable to antisera against PSOP25 antigen alone.

CONCLUSIONS

PSOP26 plays a critical role in the zygote-to-ookinete developmental transition. PSOP25 is a promising TBV candidate that could be used alone to target the ookinete stage.

摘要

背景

疟原虫合子到卵囊发育期的转变是在蚊媒中建立感染的关键步骤，在此阶段表达的抗原是传播阻断疫苗（TBV）的潜在靶点。分泌的卵囊蛋白 26（PSOP26）是一种新鉴定的卵囊表面蛋白。抗 PSOP26 血清具有中等的传播阻断活性，表明进一步研究该蛋白作为 TBV 靶标是有益的。

方法

通过靶向基因敲除分析 psop26 的功能。在大肠杆菌系统中表达嵌合 PSOP25-PSOP26 蛋白。使用 PSOP25-PSOP26 融合蛋白以及混合（PSOP25+PSOP26）或单一蛋白（PSOP26 或 PSOP25）对小鼠进行免疫。通过酶联免疫吸附试验（ELISA）、间接免疫荧光法（IFA）和 Western blot 分析个体血清的抗体滴度和免疫原性。使用体外和体内试验评估不同免疫方案血清的传播阻断活性。

结果

PSOP26 是一种在疟原虫配子和卵囊期表达的表面蛋白。该蛋白对于无性血期发育、配子发生和合子形成不是必需的，但对于合子到卵囊发育期的转变是必需的。具体来说，在感染 psop26 缺失突变体的蚊子中，感染的流行率和卵囊密度均降低。单个 PSOP25 和 PSOP26 片段（PSOP25+PSOP26）的混合物以及嵌合体（PSOP25-PSOP26）在小鼠中引起高抗体水平，没有免疫干扰。针对混合和融合蛋白的抗血清比针对单一 PSOP26 抗原的抗血清引起更高的传播减少活性（TRA），但与单独针对 PSOP25 抗原的抗血清相当。