流感病毒疫苗研究现状、发展趋势和展望

 流感大流行严重威胁人类的生命健康和社会经济的发展。及时提供充足、有效的流感疫苗是目前各国应对流感大流行的首选方法。然而,目前流感疫苗还存在许多问题,如生产周期长、保护范围有限（不具备广谱性）、易产生过敏反应等。为此,各国政府和科研团体都在进行着不懈的努力以应对流感的大流行。本文介绍了目前国内外使用的流感疫苗,比较了流感灭活疫苗和减毒活疫苗的优缺点;针对当前流感病毒疫苗研制中亟待解决的问题,即疫苗的保护时效及合适的培养基问题,探讨了解决的思路以及取得的进展;结合中国在流感方面的主要研究进展,探讨了中国流感病毒疫苗相关基础研究中需要解决的关键科学问题,并对未来流感的防控进行了展望。     

接种疫苗防流感

<正>又到秋冬之交,我国很多地方开始进入流感高发期。流感是由不同类型的流感病毒引起的,历史上的流感大流行曾经造成数千万人的死亡。接种流感疫苗是控制与预防流感大规模流行的有效办法。     

甲流症状与新冠有哪些区别? 如何预防?

<正>近日,北京、上海、天津、浙江等地部分学校因学生发热而停课,发热原因为甲型流感。目前甲流、诺如病毒感染已经进入高发期,孩子出现发烧等症状,不一定是由新冠病毒引起的。什么是流感?有哪些症状?传播途径是什么?学校和托幼机构如何预防?什么是流感?流行性感冒(简称流感)是流感病毒引起的一种急性呼吸道传染病。流感病毒分为甲、乙、丙、丁4型,人流感主要是甲型流感病毒和乙型流感病毒引起。甲型和乙型流感每年呈季节性流行,其中甲型流感易引起大流行。     

我国防控突发疫情能力跨越发展 自主抗流感药物战略储备充足

正"在科技重大专项支持下,我国创新药物应急研发能力取得重大突破,奥司他韦(口服)、帕拉米韦(静脉输液)、扎那米韦(吸入)等神经氨酸酶抑制剂成为流感的有效治疗药物,患病早期尤其是发病48小时之内及时应用抗流感病毒药物,能显著降低流感重症和死亡的发生率。"3月27日,科技部召开"艾滋病和病毒性肝炎等重大传染病防治"科技重大专项成果发布会,传染病专项技术副总师徐建国院士透露,目前我国在抗流感病毒药物的研发生产方面可自主满足临床需求,由军事医学科学院和深圳市东阳光实业     

流感疫苗的研究进展

流感是一种严重危害人类健康的传染病,目前接种传统的鸡胚灭活疫苗仍是预防流感的主要措施.近几年,生产工艺先进、副作用小的新型流感类病毒颗粒疫苗、重组活载体疫苗、病毒核酸疫苗和广谱疫苗的研究均有突破性进展,尤其基于MDCK细胞和Vero细胞等哺乳动物细胞培养的流感疫苗在欧美国家已经上市,有替代传统疫苗的趋势.     

如何预防流感最有效

正2018年的流感来势汹汹,全国监测数据显示哨点医院报告流感病例高于过去三年同期水平。据世界卫生组织表示,接种疫苗是预防流感的最有效方法。季节性流感病毒季节性流感病毒分为甲型、乙型和丙型三种,其中丙型流感对公共卫生影响较小,甲型和乙型流感病毒的传播易导致流行和疫情。根据血凝素(H)和神经氨酸酶(N)的结合情况,甲型流感病毒又进     

从科幻小说到科学发现

这半个月来,占据各大媒体版面头条的新闻仍旧是甲型H1N1病毒流感.5月11日,四川省确诊中国内地首例甲型H1N1流感病例,此后山东、北京、西藏也相继出现确诊病例.半月来流感疫情的发展仍令人忧心,世卫组织(WHO)5月12日表示,甲型H1N1流感病毒还可能继续变异成毒性更强的病毒,引发流感大暴发,足以在全球引起三波疫情.WHO在<流感疫情严重程度评估>报告中写道,甲型H1N1流感病毒"似乎比季节性流感的传染性更强",而且几乎所有种族对其都没有免疫力.     

抗流感“兵器谱”

人们和流感的战争已经延续了上千年。自从人类开始使用抗病毒药物和流感疫苗以来，胜利的天平仿佛一度向人类倾斜，但是在“狡猾善变”的流感病毒面前，这些“武器”一不小心就“哑火”了。在凶猛的病毒大军到来之时，我们还有哪些看家“武器”呢？     

环己烯类神经氨酸酶抑制剂的三维定量构效关系研究

环己烯类神经氨酸酶抑制剂是目前效果最好的流感病毒抑制剂.选取26个典型的环己烯类神经氨酸酶抑制剂,应用比较分子力场分析(CoMFA)方法,研究它们与神经氨酸酶(NA)的相互作用,建立了环己烯类NA抑制剂与NA的三维定量构效关系(3D-QSAR)模型.该模型的最佳非交叉验证系数R2为0.991,交叉验证系数R2cv为0.760,检测值F为521.53,标准偏差SEE为0.098,立体场、静电场的贡献分别为74.6%、25.4%,最佳主成分为4,这表明模型具有很强的稳定性和预测能力.用该模型对随机挑选的3个化合物进行预测,得到了满意的结果.     

禽流感病毒的变异与效应

流感病毒抗原变异与流感的流行大小、预防、控制密切相关.近年来分子生物学技术的发展,越来越多的新方法、新技术用于流感病毒抗原变异的研究,本文对近年来流感病毒抗原变异的原因及其引起的效应作一扼要综述.     

Special features of the 2009 pandemic swine-origin influenza A H1N1 hemagglutinin and neuraminidase

Since the 2009 pandemic H1N1 swine-origin influenza A virus (09 S-OIV) has reminded the world about the global threat of the ever changing influenza virus,many questions regarding the detailed re-assortment of influenza viruses yet remain unanswered.Influenza A virus is the causative agent of the pandemic flu and contains 2 major antigenic glycoproteins on its surface:(i) hemagglutinin (HA);and (ii) neuraminidase (NA).The structures of the 09 S-OIV HA and NA proteins (09H1 and 09N1) have recently been resolved in our laboratory and provide some clues as to why the 09 S-OIV re-assortment virus is highly infectious with severe consequences in humans.For example,the 09H1 is highly similar to the HA of the 1918 influenza A pandemic virus in overall structure and especially in regards to its 5 defined antibody binding epitopes.For 09N1,its most distinctive feature is the lack of a 150-loop active site cavity,which was previously predicted to be present in all N1 NAs,and we hypothesize that the 150-loop may play a important role in the substrate specificity (α2,3 or α2,6 linked sialic acid receptors) and enzymatic mechanism of influenza NA.Combination of the HA and NA with special characteristics for the 09 S-OIV might contribute to its high increased transmissibility in humans.     

玉溪市2009～2012年流感哨点监测流行病学和病原学分析

目的：分析玉溪市2009~2012年流感哨点医院ILI（流感样病例）监测结果,探索流感流行特征及规律,为制定预防和控制策略提供依据;方法对2009-2012年国家流感监测哨点医院发热门诊流感样病例（ILI）进行流行病学分布研究,通过实验室分离培养流感病毒,并对流感病毒型别检测和分析;结果2009~2012年,ILI占门诊总数百分率平均为4.25%,年平均采样数为762,标本占ILI百分率平均为6.56%,每年1~3月、10~12月呈现两个发病高峰,ILl主要集中青壮年人群,职业分布以农民和学生为主,流感病毒型别流行特点：2009~2010年以新型甲型H1N1流行为主,2010~2011年以B型流感Victory系列流行为主,2012年以季节流感H3N2l流行为主;结论对玉溪市2009~2012年流感病毒的监测,发现具有时间、人群和不同型别的流行特点,结合实验室结果科学合理地使用疫苗,积极预防和控制流感病毒的流行。     

禽流感与防疫

禽流感是一种由A型流感病毒的一种亚型(也称禽流感病毒)引起的禽类(家禽和野禽)和人的传染性疾病,被国际兽疫局定为甲类传染病,了解和认识禽流感的流行与病毒特点、传播途径、主要症状、扑灭措施及疫苗预防,对于控制和防止禽流感的发生,以及为人类健康都有着重大意义。     

普通棉耳狨猴中乙型流感病毒的分离和鉴定

乙型流感病毒是引起人类局部流行性感冒的重要病原体，其起源和自然储存宿主目前仍不清楚。1999年夏季在某动物中心饲养的普通棉耳绒猴（Callithrix jacchus）群体中爆发了以呼吸道症状为主的急性传染病，死亡比率高达1／3。通过对死亡狨猴肺组织匀浆接种鸡胚和MDCK细胞的分离培养，分离出病毒。双份血清的红细胞凝集抑制试验证实，此分离株为此次狨猴群体感染流行的病原体。通过甲型和乙型流感病毒标准血清鉴定，证实该分离株为乙型流感病毒，命名为B/marmoset/China/1/99。     

Large-scale sequencing of human influenza reveals the dynamic nature of viral genome evolution

Influenza viruses are remarkably adept at surviving in the human population over a long timescale. The human influenza A virus continues to thrive even among populations with widespread access to vaccines, and continues to be a major cause of morbidity and mortality. The virus mutates from year to year, making the existing vaccines ineffective on a regular basis, and requiring that new strains be chosen for a new vaccine. Less-frequent major changes, known as antigenic shift, create new strains against which the human population has little protective immunity, thereby causing worldwide pandemics. The most recent pandemics include the 1918 'Spanish' flu, one of the most deadly outbreaks in recorded history, which killed 30-50 million people worldwide, the 1957 'Asian' flu, and the 1968 'Hong Kong' flu. Motivated by the need for a better understanding of influenza evolution, we have developed flexible protocols that make it possible to apply large-scale sequencing techniques to the highly variable influenza genome. Here we report the results of sequencing 209 complete genomes of the human influenza A virus, encompassing a total of 2,821,103 nucleotides. In addition to increasing markedly the number of publicly available, complete influenza virus genomes, we have discovered several anomalies in these first 209 genomes that demonstrate the dynamic nature of influenza transmission and evolution. This new, large-scale sequencing effort promises to provide a more comprehensive picture of the evolution of influenza viruses and of their pattern of transmission through human and animal populations. All data from this project are being deposited, without delay, in public archives.     

通过载体表达siRNAs抑制禽流感病毒复制的研究

禽流感病毒是养禽业危害最严重的病原微生物之一。为探讨小干涉RNA(siRNA)对A型禽流感病毒复制的干扰作用,以H5亚型AIV PB2基因为靶序列,设计合成了4对编码siRNAs的DNA序列,将其克隆到psiRNA-hH1neo载体中,构建siRNAs表达载体,鉴定正确后将重组质粒转染MDCK细胞,采用G418筛选建立抗性细胞系,用血凝(HA)试验和real time RT-PCR试验检测抑制效果, 在细胞水平筛选出具有高效抑制AIV复制的2个靶位点PB2-1154、PB2-342、为AIV的基因功能研究,抗病毒药物的开发和转基因动物的研究奠定了基础。     

禽流感病毒通用型荧光定量PCR检测试剂盒比对结果分析

对6种禽流感病毒通用型荧光定量聚合酶链式反应(polymerase chain reaction),PCR检测试剂盒进行比对与科学评价,为实验室采购提供依据。利用禽流感病毒H5、H7、H9亚型标准品,鸡新城疫活疫苗与传染性支气管炎活疫苗对市售的6种品牌(分别记为A、B、C、D、E、F)禽流感病毒通用型荧光定量PCR检测试剂盒灵敏性与特异性进行了比对,并对97份临床样品进行了检测,筛选出禽流感病毒通用型最佳检测试剂盒。结果表明:A厂家试剂盒最低可检出1:100倍稀释的H7亚型标准品浓度,B厂家试剂盒最低可检出1:1倍稀释的H7亚型标准品浓度,C厂家试剂盒最低可检出1:10倍稀释的H7亚型标准品浓度,D厂家试剂盒最低可检出1:10倍稀释的H7亚型标准品浓度,E厂家试剂盒最低可检出1:1 000倍稀释的H7亚型标准品浓度, F厂家试剂盒最低可检出1:10倍稀释的H7亚型标准品浓度,6种试剂盒特异性均良好。综上,E厂家试剂盒优于其他厂家试剂盒,可以作为动物疫病检测实验室在实施监测任务中的首要选择。     

The mechanism by which influenza A virus nucleoprotein forms oligomers and binds RNA

Influenza A viruses pose a serious threat to world public health, particularly the currently circulating avian H5N1 viruses. The influenza viral nucleoprotein forms the protein scaffold of the helical genomic ribonucleoprotein complexes, and has a critical role in viral RNA replication. Here we report a 3.2 A crystal structure of this nucleoprotein, the overall shape of which resembles a crescent with a head and a body domain, with a protein fold different compared with that of the rhabdovirus nucleoprotein. Oligomerization of the influenza virus nucleoprotein is mediated by a flexible tail loop that is inserted inside a neighbouring molecule. This flexibility in the tail loop enables the nucleoprotein to form loose polymers as well as rigid helices, both of which are important for nucleoprotein functions. Single residue mutations in the tail loop result in the complete loss of nucleoprotein oligomerization. An RNA-binding groove, which is found between the head and body domains at the exterior of the nucleoprotein oligomer, is lined with highly conserved basic residues widely distributed in the primary sequence. The nucleoprotein structure shows that only one of two proposed nuclear localization signals are accessible, and suggests that the body domain of nucleoprotein contains the binding site for the viral polymerase. Our results identify the tail loop binding pocket as a potential target for antiviral development.     

Genomic analysis of increased host immune and cell death responses induced by 1918 influenza virus

The influenza pandemic of 1918-19 was responsible for about 50 million deaths worldwide. Modern histopathological analysis of autopsy samples from human influenza cases from 1918 revealed significant damage to the lungs with acute, focal bronchitis and alveolitis associated with massive pulmonary oedema, haemorrhage and rapid destruction of the respiratory epithelium. The contribution of the host immune response leading to this severe pathology remains largely unknown. Here we show, in a comprehensive analysis of the global host response induced by the 1918 influenza virus, that mice infected with the reconstructed 1918 influenza virus displayed an increased and accelerated activation of host immune response genes associated with severe pulmonary pathology. We found that mice infected with a virus containing all eight genes from the pandemic virus showed marked activation of pro-inflammatory and cell-death pathways by 24 h after infection that remained unabated until death on day 5. This was in contrast with smaller host immune responses as measured at the genomic level, accompanied by less severe disease pathology and delays in death in mice infected with influenza viruses containing only subsets of 1918 genes. The results indicate a cooperative interaction between the 1918 influenza genes and show that study of the virulence of the 1918 influenza virus requires the use of the fully reconstructed virus. With recent concerns about the introduction of highly pathogenic avian influenza viruses into humans and their potential to cause a worldwide pandemic with disastrous health and economic consequences, a comprehensive understanding of the global host response to the 1918 virus is crucial. Moreover, understanding the contribution of host immune responses to virulent influenza virus infections is an important starting point for the identification of prognostic indicators and the development of novel antiviral therapies.