关键词： 脊髓灰质炎   口服脊髓灰质炎减毒活疫苗   灭活脊髓灰质炎病毒疫苗   免疫策略  

摘要： 脊髓灰质炎（脊灰）疫苗可以有效预防脊灰的发生。随着全球消灭脊灰目标的即将实现,后脊灰时代的免疫策略备受关注。本文对脊灰疫苗接种现状、全球及中国消灭脊灰进程及免疫策略等方面进行了综述,探索脊灰疫苗接种由口服脊灰减毒活疫苗（OPV）向灭活脊灰病毒疫苗（IPV）转换过程中可能存在的问题,为长期的免疫策略提供参考依据。

关键词： 脊髓灰质炎后遗症   脊髓灰质炎后综合征   跌倒   风险因素   预防   综述  

摘要： 跌倒和跌倒有关的伤害是脊髓灰质炎后遗症及脊髓灰质炎后综合征(PPS)患者常见且重要的问题。患者存在一般老年人跌倒的相同危险因素,同时脊髓灰质炎后遗症及PPS引起的疲劳、肌肉和关节疼痛、不能耐受寒冷等也可能导致跌倒发生。跌倒经常导致这些患者出现身体损伤、进一步残疾以及跌倒恐惧心理,继而避免活动。为了降低脊髓灰质炎后遗症及PPS患者的跌倒发生率,应认真综合评价跌倒的发生,纠正并消除患者的错误观念,分析跌倒的原因及机制,减少风险因素,采取多学科综合性跌倒管理计划及干预措施,保持健康的生活方式,预防跌倒,避免进一步致残。

关键词： 灭活脊髓灰质炎疫苗   预防接种   异常反应  

摘要： 目的对灭活脊髓灰质炎疫苗疑似预防接种异常反应进行监测和研究。方法选择2014年2月至2017年2月期间在我院接受灭活脊髓灰质炎疫苗的患者共96例,观察并记录异常反应发生的情况,并作出相应的处理。结果在接受疫苗的96例患者中,共有79例患者未出现任何不良反应,有12例患者出现了恶心、呕吐、发热等不良反应,其中有4例患者出现了轻度腹泻的症状,并且大便呈现黄色,在两天后有所缓解。共有5例患者出现了异常反应的情况,其中2例患者出现荨麻疹、1例患者出现过敏性皮疹、2例患者出现过敏性紫癜。结论灭活脊髓灰质炎疫苗疑似预防接种异常反应发生的概率较低,对于出现的异常反应应及时进行处理,避免医疗事故。

关键词： Sabin株脊髓灰质炎病毒   透析   感染性滴度   回收率  

摘要： 目的采用透析法对Sabin株3个型别的脊髓灰质炎病毒收获液进行透析后的病毒回收效果评价。方法高病毒滴度时,对Sabin株Ⅰ、Ⅱ、Ⅲ型病毒收获液分别进行透析,比较每个型别病毒收获液透析前后的病毒感染性滴度回收率,及透析后的甲醛清除率;低病毒滴度时,选取101、100、10-1 CCID_(50)/mL 3个滴度的Sabin株Ⅰ、Ⅱ、Ⅲ型病毒液,分别进行透析,将相同型别及滴度的透析前后样品接种至Hep-2细胞上进行3次传代,比较透析前后细胞病变比率及病毒滴度。结果高病毒滴度时,各型别病毒收获液透析后与透析前相比,样品体积和感染性滴度均未发生较大变化(P>0.05),透析后甲醛清除率达99%以上。101 CCID_(50)/mL低病毒滴度时,各型别病毒3次传代均能100%引起细胞病变;100 CCID_(50)/mL低病毒滴度时,Ⅰ、Ⅱ、Ⅲ型病毒第1次传代引起细胞病变比率分别为66%、33%和33%,第2、3次传代均能100%引起细胞病变;10-1 CCID_(50)/mL低病毒滴度时,3个型别病毒3次传代均不能引起细胞病变。所有细胞病变后检测病毒滴度均在6.0 lgCCID_(50)/mL以上。结论 Sabin株3个型别的病毒收获液经透析后,活病毒的回收率较高,基本无损失,透析法可作为该病毒的纯化方法。

关键词： 脊髓灰质炎疫苗   基础免疫   替代  

摘要： 目的了解2016年宁波市鄞州区首剂脊髓灰质炎（脊灰）灭活疫苗（IPV）纳入免疫规划（EPI）对儿童脊灰疫苗（PV）基础免疫的影响。方法通过宁波市免疫规划信息管理系统收集PV免疫规划策略调整前后鄞州区3-7月龄儿童的PV基础免疫数据,比较儿童PV接种率、IPV接种替代率和免疫程序构成特征。结果 IPV纳入EPI前后鄞州区调查对象PV1接种率分别为97.70%、98.30%（OR=1.24,95%CI：1.00-1.55）,PV1-3接种率分别为89.48%、92.56%（OR=1.06,95%CI：0.96-1.16）,IPV1接种替代率为45.67%、95.17%（OR=27.13,95%CI：24.25-30.35）,IPV1-3接种替代率分别为43.11%、34.32%（OR=0.59,95%CI：0.54-0.64）。PV1免疫采用脊灰减毒活疫苗（OPV）、IPV、无细胞百白破、灭活脊灰和流感嗜血杆菌联合疫苗（DTa P-IPV/Hib）的儿童比例分别从54.33%减少到4.83%、从30.43%上升到70.77%、从15.24%上升到24.39%。PV基础免疫采用OPV-OPV-OPV、IPV-IPV-IPV、IPV-IPV-OPV程序的儿童比例下降,分别从54.09%到3.76%、从29.98%到10.49%、从1.54%到0.53%,采用IPV-OPV-OPV、3剂次DTa P-IPV/Hib、其他程序的比例增高,分别从0.89%到59.10%、从13.13%到23.83%、从0.37%到2.30%。结论首剂IPV纳入EPI对儿童IPV替代接种和PV免疫程序选择产生影响,但未对儿童PV接种率产生影响。

关键词： 破伤风类毒素   铝吸附   抗原性   指纹   脊髓灰质炎病毒   磷酸   联合疫苗   单克隆抗体  

摘要： 测定了含白喉类毒素（DTd）、破伤风类毒素和灭活脊髓灰质炎病毒的联合疫苗中明矾吸附的白喉类毒素的抗原性。使用了一组分散在DTd上的五个抗原决定簇的单克隆抗体。获得的DTd的抗原指纹显示，联合疫苗成品中其在抗原水平上有稳定性的吸附。

关键词： RNA replication   coxsackievirus   enterovirus   plus-strand RNA virus   poliovirus   proteases   proteinase   proteomics  

摘要： Enteroviruses encode proteinases that are essential for processing of the translated viral polyprotein. In addition, viral proteinases also target host proteins to manipulate cellular processes and evade innate antiviral responses to promote replication and infection. Although some host protein substrates of enterovirus proteinases have been identified, the full repertoire of targets remains unknown. We used a novel quantitative in vitro proteomics-based approach, termed terminal amine isotopic labeling of substrates (TAILS), to identify with high confidence 72 and 34 new host protein targets of poliovirus and coxsackievirus B3 (CVB3) 3C proteinases (3C(pro)s) in HeLa cell and cardiomyocyte HL-1 cell lysates, respectively. We validated a subset of candidate substrates that are targets of poliovirus 3C(pro) in vitro including three common protein targets, phosphoribosylformylglycinamidine synthetase (PFAS), hnRNP K, and hnRNP M, of both proteinases. 3C(pro)-targeted substrates were also cleaved in virus-infected cells but not noncleavable mutant proteins designed from the TAILS-identified cleavage sites. Knockdown of TAILS-identified target proteins modulated infection both negatively and positively, suggesting that cleavage by 3C(pro) promotes infection. Indeed, expression of a cleavage-resistant mutant form of the endoplasmic reticulum (ER)-Golgi vesicle-tethering protein p115 decreased viral replication and yield. As the first comprehensive study to identify and validate functional enterovirus 3C(pro) substrates in vivo, we conclude that N-terminomics by TAILS is an effective strategy to identify host targets of viral proteinases in a non-biased manner. IMPORTANCE Enteroviruses are positive-strand RNA viruses that encode proteases that cleave the viral polyprotein into the individual mature viral proteins. In addition, viral proteases target host proteins in order to modulate cellular pathways and block antiviral responses in order to facilitate virus infection. A

关键词： Immunity   Molting   Poliovirus   Vaccination and immunization   Poliomyelitis   Infectious disease epidemiology   Vaccines   Antibodies  

摘要： The oral polio vaccine (OPV) contains live-attenuated polioviruses that induce immunity by causing low virulence infections in vaccine recipients and their close contacts. Widespread immunization with OPV has reduced the annual global burden of paralytic poliomyelitis by a factor of 10,000 or more and has driven wild poliovirus (WPV) to the brink of eradication. However, in instances that have so far been rare, OPV can paralyze vaccine recipients and generate vaccine-derived polio outbreaks. To complete polio eradication, OPV use should eventually cease, but doing so will leave a growing population fully susceptible to infection. If poliovirus is reintroduced after OPV cessation, under what conditions will OPV vaccination be required to interrupt transmission? Can conditions exist in which OPV and WPV reintroduction present similar risks of transmission? To answer these questions, we built a multi-scale mathematical model of infection and transmission calibrated to data from clinical trials and field epidemiology studies. At the within-host level, the model describes the effects of vaccination and waning immunity on shedding and oral susceptibility to infection. At the between-host level, the model emulates the interaction of shedding and oral susceptibility with sanitation and person-to-person contact patterns to determine the transmission rate in communities. Our results show that inactivated polio vaccine (IPV) is sufficient to prevent outbreaks in low transmission rate settings and that OPV can be reintroduced and withdrawn as needed in moderate transmission rate settings. However, in high transmission rate settings, the conditions that support vaccine-derived outbreaks have only been rare because population immunity has been high. Absent population immunity, the Sabin strains from OPV will be nearly as capable of causing outbreaks as WPV. If post-cessation outbreak responses are followed by new vaccine-derived outbreaks, strategies to restore population immunit

关键词： Viral replication   HeLa cells   Cellular structures and organelles   Luciferase   RNA synthesis   Viral genomics   Viral structure   Transmission electron microscopy  

摘要： At the culmination of poliovirus (PV) multiplication, membranes are observed that contain phosphatidylinositol-4-phosphate (PI4P) and appear as vesicular clusters in cross section. Induction and remodeling of PI4P and membranes prior to or concurrent with genome replication has not been well studied. Here, we exploit two PV mutants, termed EG and GG, which exhibit aberrant proteolytic processing of the P3 precursor that substantially delays the onset of genome replication and/or impairs virus assembly, to illuminate the pathway of formation of PV-induced membranous structures. For WT PV, changes to the PI4P pool were observed as early as 30 min post-infection. PI4P remodeling occurred even in the presence of guanidine hydrochloride, a replication inhibitor, and was accompanied by formation of membrane tubules throughout the cytoplasm. Vesicular clusters appeared in the perinuclear region of the cell at 3 h postinfection, a time too slow for these structures to be responsible for genome replication. Delays in the onset of genome replication observed for EG and GG PVs were similar to the delays in virus-induced remodeling of PI4P pools, consistent with PI4P serving as a marker of the genome-replication organelle. GG PV was unable to convert virus-induced tubules into vesicular clusters, perhaps explaining the nearly 5-log reduction in infectious virus produced by this mutant. Our results are consistent with PV inducing temporally distinct membranous structures (organelles) for genome replication (tubules) and virus assembly (vesicular clusters). We suggest that the pace of formation, spatiotemporal dynamics, and the efficiency of the replication-to-assembly-organelle conversion may be set by both the rate of P3 polyprotein processing and the capacity for P3 processing to yield 3AB and/or 3CD proteins.

关键词： cellular responses   DNA microarray   genetic markers   infectious poliovirus   ion channels  

摘要： AimsCellular responses of an established cell line from human intestinal epithelial cells (INT-407 cells) against poliovirus (PV) infections were investigated in order to find cellular genetic markers for infectious PV detection. Methods and ResultsGene expression profile of INT-407 cells was analysed by DNA microarray technique when cells were infected with poliovirus 1 (PV1) (sabin) at multiplicity of infection of 10(-3) and incubated for 12h. Poliovirus infection significantly altered the gene expressions of two ion channels, KCNJ4 and SCN7A. The expression profile of KCNJ4 gene was further investigated by real-time RT-qPCR, and it was found that KCNJ4 gene was significantly regulated at 24h postinfection of PV1. ConclusionsKCNJ4 gene, coding a potassium channel protein, is proposed as a cellular genetic marker for infectious PV detection. Significance and Impact of the StudyThis is the first study to show the availability of cellular responses to detect infectious PV. The selection of cellular genetic markers for infectious viruses using DNA microarray and RT-qPCR can be applicable for the other enteric viruses.