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Malaria Derived Glycosylphosphatidylinositol Anchor Enhances Anti-Pfs25 Functional Antibodies That Block Malaria Transmission.
Biochemistry ( IF 2.9 ) Pub Date : 2018-01-16 , DOI: 10.1021/acs.biochem.7b01099 Neeraj Kapoor 1 , Ivana Vanjak 1 , James Rozzelle 1 , Aym Berges 1 , Wei Chan 1 , Gang Yin 2 , Cuong Tran 2 , Aaron K Sato 2 , Alexander R Steiner 2 , Thao P Pham 3 , Ashley J Birkett 4 , Carole A Long 3 , Jeff Fairman 1 , Kazutoyo Miura 3
Biochemistry ( IF 2.9 ) Pub Date : 2018-01-16 , DOI: 10.1021/acs.biochem.7b01099 Neeraj Kapoor 1 , Ivana Vanjak 1 , James Rozzelle 1 , Aym Berges 1 , Wei Chan 1 , Gang Yin 2 , Cuong Tran 2 , Aaron K Sato 2 , Alexander R Steiner 2 , Thao P Pham 3 , Ashley J Birkett 4 , Carole A Long 3 , Jeff Fairman 1 , Kazutoyo Miura 3
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Malaria, one of the most common vector borne human diseases, is a major world health issue. In 2015 alone, more than 200 million people were infected with malaria, out of which, 429 000 died. Even though artemisinin-based combination therapies (ACT) are highly effective at treating malaria infections, novel efforts toward development of vaccines to prevent transmission are still needed. Pfs25, a postfertilization stage parasite surface antigen, is a leading transmission-blocking vaccine (TBV) candidate. It is postulated that Pfs25 anchors to the cell membrane using a glycosylphosphatidylinositol (GPI) linker, which itself possesses pro-inflammatory properties. In this study, Escherichia coli derived extract (XtractCF+TM) was used in cell free protein synthesis [CFPS] to successfully express >200 mg/L of recombinant Pfs25 with a C-terminal non-natural amino acid (nnAA), namely, p-azidomethyl phenylalanine (pAMF), which possesses a reactive azide group. Thereafter, a unique conjugate vaccine (CV), namely, Pfs25-GPI was generated with dibenzocyclooctyne (DBCO) derivatized glycan core of malaria GPI using a simple but highly efficient copper free click chemistry reaction. In mice immunized with Pfs25 or Pfs25-GPI, the Pfs25-GPI group showed significantly higher titers compared to the Pfs25 group. Moreover, only purified IgGs from Pfs25-GPI group were able to significantly block transmission of parasites to mosquitoes, as judged by a standard membrane feeding assay [SMFA]. To our knowledge, this is the first report of the generation of a CV using Pfs25 and malaria specific GPI where the GPI is shown to enhance the ability of Pfs25 to elicit transmission blocking antibodies.
中文翻译：
疟疾衍生的糖基磷脂酰肌醇锚可以增强阻止疟疾传播的抗Pfs25功能抗体。
疟疾是人类最常见的媒介传播疾病之一，是世界主要的健康问题。仅在2015年，就有2亿多人感染了疟疾，其中429 000例死亡。尽管基于青蒿素的联合疗法（ACT）在治疗疟疾感染方面非常有效，但仍需要在开发疫苗以预防传播方面做出新的努力。Pfs25是受精后阶段的寄生虫表面抗原，是领先的阻断传播疫苗（TBV）候选者。据推测，Pfs25使用糖基磷脂酰肌醇（GPI）接头锚定到细胞膜上，该接头本身具有促炎特性。在这项研究中，大肠杆菌提取物（XtractCF + TM）用于无细胞蛋白质合成[CFPS]中，可成功表达> 具有C端非天然氨基酸（nnAA）的200 mg / L重组Pfs25，即具有反应性叠氮基的对叠氮基甲基苯丙氨酸（pAMF）。此后，使用简单但高效的无铜点击化学反应，用二苯并环辛炔（DBCO）衍生的疟疾GPI聚糖核心生成了独特的偶联疫苗（CV），即Pfs25-GPI。在用Pfs25或Pfs25-GPI免疫的小鼠中，Pfs25-GPI组的滴度明显高于Pfs25组。此外，根据标准的膜饲喂测定法[SMFA]判断，只有来自Pfs25-GPI组的纯化IgG才能显着阻断寄生虫向蚊子的传播。据我们所知，
更新日期：2018-01-16
中文翻译：
疟疾衍生的糖基磷脂酰肌醇锚可以增强阻止疟疾传播的抗Pfs25功能抗体。
疟疾是人类最常见的媒介传播疾病之一，是世界主要的健康问题。仅在2015年，就有2亿多人感染了疟疾，其中429 000例死亡。尽管基于青蒿素的联合疗法（ACT）在治疗疟疾感染方面非常有效，但仍需要在开发疫苗以预防传播方面做出新的努力。Pfs25是受精后阶段的寄生虫表面抗原，是领先的阻断传播疫苗（TBV）候选者。据推测，Pfs25使用糖基磷脂酰肌醇（GPI）接头锚定到细胞膜上，该接头本身具有促炎特性。在这项研究中，大肠杆菌提取物（XtractCF + TM）用于无细胞蛋白质合成[CFPS]中，可成功表达> 具有C端非天然氨基酸（nnAA）的200 mg / L重组Pfs25，即具有反应性叠氮基的对叠氮基甲基苯丙氨酸（pAMF）。此后，使用简单但高效的无铜点击化学反应，用二苯并环辛炔（DBCO）衍生的疟疾GPI聚糖核心生成了独特的偶联疫苗（CV），即Pfs25-GPI。在用Pfs25或Pfs25-GPI免疫的小鼠中，Pfs25-GPI组的滴度明显高于Pfs25组。此外，根据标准的膜饲喂测定法[SMFA]判断，只有来自Pfs25-GPI组的纯化IgG才能显着阻断寄生虫向蚊子的传播。据我们所知，
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