一、研究新知
Minipool caprylic acid fractionation of plasma using disposable equipment: a practical method to enhance immunoglobulin supply in developing countries
Magdy El-Ekiaby, Mariángela Vargas, Makram Sayed, George Gorgy, Hadi Goubran, Mirjana Radosevic, Thierry Burnouf
PLOS Neglected Tropical Diseases, 2015; 9 (2): e0003501, DOI: 10.1371/journal.pntd.0003501
伊波拉病毒肆虐非洲，造成賴比瑞亞、獅子山共和國等西非國家近萬人死亡，目前雖有免疫球蛋白用於治療，但研發過程繁複且成本高。免疫球蛋白G（IgG）是世衛組織抗病毒基本藥物，但也是發展中國家缺乏的重要血漿衍生的藥物。發展中國家面臨治療物質嚴重短缺，IgG的短缺讓免疫缺陷的患者無法接受治療，並且暴露在當地病原體反覆感染。法國科學家Thierry Burnouf長期致力於血液製品工程及病毒安全性研究，他指出，一般製備血漿免疫球蛋白，需要繁複步驟、高成本及製藥等級設備，在研究團隊努力下，研發出簡單方式，這個方式是種封閉式且一次性使用醫療設備。Thierry Burnouf與埃及醫院研究團隊，發現只要在封閉式的塑膠製血袋，加入化學試劑「辛酸」，經過充分搖晃1小時，再離心取出上清液，利用透析移除辛酸、濃縮和過濾等步驟，即可製成免疫球蛋白，成果已刊登於PLOS Neglected Tropical Diseases -Minipool Caprylic Acid Fractionation of Plasma Using Disposable Equipment: A Practical Method to Enhance Immunoglobulin Supply in Developing Countries。對於對抗類似伊波拉病毒的疫病傳染，只要從感染而僥倖存活下來者身上，取得血漿製成免疫球蛋白，輸注到感染者體內就能對抗病毒，這套系統已獲得非洲慈善機構Global Emerging Pathogen(GEP)青睞和非洲血液中心同意，GPE獲比爾蓋茲基金會贊助，決定採用這套製備免疫球蛋白的方法，作為下次伊波拉病毒來襲時，降低傷亡的緊急救援措施。全文請連結http://journals.plos.org/plosntds/article?id=10.1371/journal.pntd.0003501與相關聯結http://www.sciencedaily.com/releases/2015/02/150226144901.htm。
英文摘要
Plasma-derived immunoglobulin G (IgG) is on WHO’s Essential Medicines List, yet developing countries face severe shortages of this critical treatment. Infusion of IgG prepared from locally-collected plasma provides an advantageous mix of antibodies to viral and bacterial pathogens found in the living environment, and this can reduce recurrent infections in immune-deficient patients. We developed a simple manufacturing process using disposable equipment (blood bags, hemodialyzer, and filters) to isolate immunoglobulins from minipools of 20 plasma donations. This process yields a ca. 90% pure virally-inactivated immunoglobulin fraction at 50–60% recovery. Anti-hepatitis B and anti-rubella immunoglobulins were enriched fourfold to sixfold. The product was free of in-vitro thrombogenic and proteolytic activity, confirming its expected clinical safety profile. Virus validations showed caprylic acid treatment robustly inactivated or removed infectivity of lipid-enveloped viruses, including human immunodeficiency virus (HIV) and hepatitis C virus model. This simple and cost-effective process is implemented in Egypt to prepare experimental batches for clinical evaluation. It can enhance immunoglobulin supplies to treat immunodeficient patients through passive transmission of antibodies directed against local pathogens. The method requires minimal training and reasonable infrastructure, and is a practical means to prepare convalescent hyperimmune IgG during infectious outbreaks such as the current Ebola episode.