埃博拉疫苗和药物研究进展

埃博拉病毒(Ebola virus)是丝状病毒科的一员,可导致埃博拉出血热,致死率达25%~90%不等。2014年暴发的埃博拉疫情席卷了西非各地,极高的致死率引起了全世界的恐慌。鉴于埃博拉病毒严重威胁人类公共健康,科学研究毫无懈怠,多种疫苗如rVSV-ZEBOV和ChAd3-ZEBOV等已经进入临床试验阶段,多种药物如TKMEbola和ZMapp等已用于埃博拉患者的紧急治疗。本文总结了近期埃博拉疫苗和药物的最新研究进展。     

埃博拉病毒疫苗研究进展及相关专利浅析

通过非专利数据库的文献检索,总结了埃博拉病毒（EBOV）研究的最新进展,通过专利文献数据库文献检索分析EBOV疫苗的专利申请基本情况、发展趋势和技术点。结果发现专利申请量与疫情的爆发有一定的相关性;专利申请人多为政府主导的机构或非营利性机构;最新的专利申请均关注GP蛋白对病毒侵染的重要性,针对GP蛋白的抗体和疫苗正在开发中,其中Mapp生物制药公司的产品“ZMapp”作为试验性生物药物目前效果最佳。     

埃博拉病毒疫苗rVSV-ZEBOV的研究进展

埃博拉病毒被列为A类病原体,感染后可引起埃博拉出血热,具有高传染率和高致死率。研发安全有效的抗病毒疫苗迫在眉睫。目前正在研发的埃博拉病毒疫苗包括病毒载体疫苗、蛋白疫苗、DNA疫苗等,其中最有希望的是重组水疱性口炎病毒载体疫苗rVSV-ZEBOV。该疫苗在预防和治疗埃博拉出血热方面具有较高的安全性和有效性,有望在2018年上市。为了深入了解rVSV-ZEBOV疫苗,现主要从制备方法、药理学研究和作用机制等方面对该疫苗进行介绍。     

埃博拉病毒疫苗和药物的研发进展及启示

2014年空前的西非埃博拉疫情,使得埃博拉病毒受到了全世界的广泛关注。针对埃博拉病毒病,目前还没有获批上市的疫苗和药物,但有几种疫苗和药物已在非人灵长类动物中证实了保护效果,其中少数品种已进入临床试验阶段。本文集中介绍几种最具前景的疫苗和药物,并对其发展前景进行了分析和预测。     

表达埃博拉病毒表面糖蛋白的rVSV载体疫苗的效力与效果

正以表达扎伊尔埃博拉病毒表面糖蛋白的重组、可复制水泡性口炎病毒为基础的疫苗(rV SV-ZEBOV)是有希望的埃博拉病毒候选疫苗。本文主要描述了在西非的几内亚地区所做临床试验临时分析的结果。此次标签开放、群随机的环状疫苗接种实验,Basse-Guinée(几内亚,西非)的埃博拉病毒疑似病例由国家检测系统的埃博拉应急小组独立进行确诊。     

埃博拉病毒及其致病机制

自2014年2~3月,西非埃博拉病毒感染的暴发流行已呈播散趋势,受到世界卫生组织的高度重视。我国也提高了防止埃博拉病毒进入国内的警示,并采取了相应措施。现将有关埃博拉病毒的生物学特性、致病机制及相关流行病学与防治策略作简要综述,供参考。     

Epitopes of Naturally Acquired and Vaccine‐Induced Anti‐Ebola Virus Glycoprotein Antibodies in Single Amino Acid Resolution

The Ebola virus (EBOV) can cause severe infections in humans, leading to a fatal outcome in a high percentage of cases. Neutralizing antibodies against the EBOV surface glycoprotein (GP) can prevent infections, demonstrating a straightforward way for an efficient vaccination strategy. Meanwhile, many different anti‐EBOV antibodies have been identified, whereas the exact binding epitopes are often unknown. Here, the analysis of serum samples from an EBOV vaccine trial with the recombinant vesicular stomatitis virus‐Zaire ebolavirus (rVSV‐ZEBOV) and an Ebola virus disease survivor, using high‐density peptide arrays, is presented. In this proof‐of‐principle study, distinct IgG and IgM antibodies binding to different epitopes of EBOV GP is detected: By mapping the whole GP as overlapping peptide fragments, new epitopes and confirmed epitopes from the literature are found. Furthermore, the highly selective binding epitope of a neutralizing monoclonal anti‐EBOV GP antibody could be validated. This shows that peptide arrays can be a valuable tool to study the humoral immune response to vaccines in patients and to support Ebola vaccine development.     

Association of polyadenylic acid with messenger RNA of vesicular stomatitis virus

Polyadenylate (poly(A)) sequences are associated with the 28 S and 13–15 S messenger RNA species of vesicular stomatitis virus. These sequences contain approximately 125 to 150 nucleotides. Virion RNA contains little or no poly(A) sequences. The association of poly(A) with viral messenger RNA species and the gross distribution of poly(A) among these species remain unaltered even when the RNA is synthesized in the presence of cordycepin or cycloheximide and whether viral messenger RNA is polyribosome-bound or free. Also, when viral translation is completely inhibited by superinfection with poliovirus, there is no effect on poly(A) association with the messenger RNA of vesicular stomatitis virus.     

埃博拉病毒/埃博拉病—2014

2014年2月,死亡率极高的埃博拉病(EVD)开始在西部非洲的几内亚暴发流行,接下来,暴发流行出现在塞拉利昂、利比里亚、尼日利亚和塞内加尔另四个西部非洲的国家。现在,几内亚、利比里亚和塞拉利昂的疫情最重。迄今为止,已有4 784人患EVD,且人数仍在倍增,这次暴发流行已成为自40年前EVD被发现以来规模最大的一次,已形成了波及其他地区和国家的巨大危险。在此,综述2014年EVD暴发流行的起因,埃博拉病毒(EBOV)及其传播,EVD的诊断治疗,EBOV疫苗的研制以及EBOV感染的防控。     

The structure of vesicular stomatitis virus membrane A phosphorus nuclear magnetic resonance approach

The proton decoupled 40.48 M Hz ³¹P NMR spectrum of intact and unperturbed membrane-enclosed vesicular stomatitis virus (serotype Indiana) exhibited two distinct maxima. These can be resolved into a narrow, symmetric line and a broad asymmetric line. The ³¹P NMR spectrum of a multilamellar (unsonicated) preparation of the extracted viral lipids exhibited a line shape similar to that of the intact virus. A sonicated vesicle preparation of the extracted viral lipids exhibited a narrow symmetric line. The narrow component in the intact virus spectrum may be attributed to small membrane fragments. Phospholipase C digestion of the intact virus resulted in substantial reduction in intensity of both components which suggests that much of the contribution to both peaks is due to phosphate in the phospholipid polar head groups.The phospholipid phosphates in both sonicated and unsonicated preparations of the extracted viral lipids exhibited substantially longer relaxation times than did those in the intact virus. The short relaxation time emanating from the intact virus preparation is caused by immobilization of the phospholipid head groups which could be due to lipid-protein interactions. Trypsin treatment of vesicular stomatitis virions, which results in complete removal of the exterior hydrophilic segment of the membrane glycoprotein, increased the ³¹P relaxation time to a value similar to that observed in the protein-free total lipid extracts; this finding provides supporting evidence for the role of virus glycoprotein in shortened relaxation times. A reversible temperature-dependent change in apparent line width and absence of an effect of cholesterol on the ³¹P phospholipid spectrum were also demonstrated.     

Assembly of the vesicular stomatitis virus envelope: incorporation of viral polypeptides into the host plasma membrane

Incorporation of viral polypeptides into the host plasma membrane is an essential step in the formation of the lipoprotein envelope of vesicular stomatitis virus. A quantitative study of this process was carried out using a double-isotope labeling procedure. Infected cells were incubated for two hours with ¹⁴C-labeled amino acids, pulse-labeled with [³H]leucine and incubated for various times with an excess of non-radioactive leucine. The ${}^3\text{H}{}^{14}\text{C}$ ratio was determined for each viral polypeptide in isolated plasma membranes and in the whole cell by polyacrylamide gel electrophoresis. It was found that [³H]leucine-labeled viral polypeptides could be detected in the plasma membranes immediately following a 30-second pulse but that the ${}^3\text{H}{}^{14}\text{C}$ ratios of polypeptides in the plasma membrane did not reach the ${}^3\text{H}{}^{14}\text{C}$ ratios in the whole cells until the end of a two-minute chase period. The addition of puromycin to the cultures at the end of the pulse period did not affect subsequent incorporation of [³H]leucine-labeled polypeptides into the plasma membrane. The incorporation of various amino acid analogs into the viral polypeptides did not affect the efficiency with which they were incorporated into the plasma membranes. It is proposed that viral polypeptides are selected for incorporation into the plasma membrane from a small interior pool of completed molecules.     

Development of therapeutics for treatment of Ebola virus infection

Ebola virus infection can cause Ebola virus disease (EVD). Patients usually show severe symptoms, and the fatality rate can reach up to 90%. No licensed medicine is available. In this review, development of therapeutics for treatment of Ebola virus infection and EVD will be discussed.     

埃博拉出血热及埃博拉病毒的研究进展

埃博拉病毒可以引起一种人畜共患烈性传染病,即埃博拉出血热,此病于1976年始发于埃博拉河流域,并且于该区域严重流行,故而得名。人类一旦感染埃博拉病毒,死亡率可高达88%,从而引起医学界的广泛关注,世界卫生组织已将埃博拉病毒列为对人类危害最为严重的病毒之一。深入地了解埃博拉出血热及埃博拉病毒,及其致病机理,对于埃博拉出血热的预防和控制具有非常重要的意义。     

埃博拉病毒的生态学

埃博拉病毒疫情正在西非一些国家蔓延,成为历史上最大的一次埃博拉病毒流行,在当地造成极大损失,也对世界各国的公共卫生安全构成严重威胁。本文介绍了埃博拉病毒暴发流行的历史和特点、在自然界的贮存宿主、传播特征等方面研究的进展,以及需要重点关注的问题。     

Identification of Ebola virus microRNAs and their putative pathological function

Ebola virus(EBOV),a member of the filovirus family,is an enveloped negative-sense RNA virus that causes lethal infections in humans and primates.Recently,more than 1000 people have been killed by the Ebola virus disease in Africa,yet no specific treatment or diagnostic tests for EBOV are available.In this study,we identified two putative viral microRNA precursors(pre-miRNAs)and three putative mature microRNAs(miRNAs)derived from the EBOV genome.The production of the EBOV miRNAs was further validated in HEK293T cells transfected with a pcDNA6.2-GW/EmGFP-EBOV-pre-miRNA plasmid,indicating that EBOV miRNAs can be produced through the cellular miRNA processing machinery.We also predicted the potential target genes of these EBOV miRNAs and their possible biological functions.Overall,this study reports for the first time that EBOV may produce miRNAs,which could serve as non-invasive biomarkers for the diagnosis and prognosis of EBOV infection and as therapeutic targets for Ebola viral infection treatment.