Immunology Department, Malaria Vaccine and Drug Development Center, Cali, Colombia.
Immunology Department, Caucaseco Scientific Research Center, Cali, Colombia.
Front Immunol. 2021 Jun 24;12:634738. doi: 10.3389/fimmu.2021.634738. eCollection 2021.
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.
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。