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来自低度到中度疟疾流行地区血清对在 和中国仓鼠卵巢系统中产生的 r48/45 蛋白的免疫反应性。

Immunoreactivity of Sera From Low to Moderate Malaria-Endemic Areas Against r48/45 Proteins Produced in and Chinese Hamster Ovary Systems.

机构信息

Immunology Department, Malaria Vaccine and Drug Development Center, Cali, Colombia.

Immunology Department, Caucaseco Scientific Research Center, Cali, Colombia.

出版信息

Front Immunol. 2021 Jun 24;12:634738. doi: 10.3389/fimmu.2021.634738. eCollection 2021.

Abstract

P48/45 is a conserved gametocyte antigen involved in parasite fertilization. A recombinant P48/45 (48/45) protein expressed in () was highly antigenic and immunogenic in experimental animals and elicited specific transmission-blocking (TB) antibodies in a previous pilot study. Here, a similar 48/45 gene was expressed in Chinese Hamster Ovary (CHO) cells and we compared its immunoreactivity with the product. Specific antibody titers were determined using plasma from Colombian individuals (n=227) living in endemic areas where both and are prevalent and from Guatemala (n=54) where is highly prevalent. In Colombia, plasma seroprevalence to CHO-48/45 protein was 46.3%, while for -48/45 protein was 36.1% (0.001). In Guatemala, the sero prevalence was 24.1% and 14.8% (0.001), respectively. Reactivity index (RI) against both proteins showed an age-dependent increase. IgG2 was the predominant subclass and the antibody avidity index evaluated by ELISA ranged between 4-6 mol/L. mosquito direct membrane feeding assays (DMFA) performed in presence of study plasmas, displayed significant parasite transmission-blocking (TB), however, there was no direct correlation between antibody titers and oocysts transmission reduction activity (%TRA). Nevertheless, DMFA with CHO 48/45 affinity purified IgG showed a dose response; 90.2% TRA at 100 μg/mL and 71.8% inhibition at 10 μg/mL. In conclusion, the CHO-r48/45 protein was more immunoreactive in most of the malaria endemic places studied, and CHO-r48/45 specific IgG showed functional activity, supporting further testing of the protein vaccine potential.

摘要

P48/45 是一种保守的配子体抗原,参与寄生虫受精。在()中表达的重组 P48/45(48/45)蛋白在实验动物中具有高度的抗原性和免疫原性,并在前瞻性初步研究中引发了特异性传播阻断(TB)抗体。在这里,类似的 48/45 基因在中华仓鼠卵巢(CHO)细胞中表达,我们比较了其与产物的免疫反应性。使用来自哥伦比亚(n=227)和危地马拉(n=54)的个体的血浆来确定特定抗体滴度,这些个体居住在流行地区,流行 和 。在哥伦比亚,针对 CHO-48/45 蛋白的血浆血清阳性率为 46.3%,而针对 -48/45 蛋白的为 36.1%(0.001)。在危地马拉,血清流行率分别为 24.1%和 14.8%(0.001)。针对两种蛋白质的反应性指数(RI)显示出与年龄相关的增加。IgG2 是主要亚类,通过 ELISA 评估的抗体亲和力指数范围在 4-6 mol/L 之间。在存在研究血浆的情况下进行的 蚊子直接膜喂养测定(DMFA)显示出显著的寄生虫传播阻断(TB),但是抗体滴度与卵囊传播减少活性(%TRA)之间没有直接相关性。然而,CHO 48/45 亲和纯化 IgG 的 DMFA 显示出剂量反应;在 100 μg/mL 时 90.2%TRA,在 10 μg/mL 时 71.8%抑制。总之,在大多数疟疾流行地区,CHO-r48/45 蛋白更具免疫反应性,CHO-r48/45 特异性 IgG 表现出功能活性,支持进一步测试该蛋白疫苗的潜力。

https://cdn.ncbi.nlm.nih.gov/pmc/blobs/532d/8264144/b8c988e70444/fimmu-12-634738-g001.jpg

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