关键词： 脊髓灰质炎疫苗   免疫实施   委员会   常规免疫   美国   咨询   脊灰减毒活疫苗   脊灰疫苗  

摘要： 1999年6月17日,美国免疫实施咨询委员会（Advisory Committee on Immunization Practices,ACIP）建议,自2000年1月1日起,美国所有的脊髓灰质炎（脊灰）疫苗均使用灭活脊灰疫苗（Inactivated Poliomyelitis Vaccine,IPV）。该政策旨在消除疫苗相关麻痹型脊灰（Vaccine-associated Paralytic Poliomyelitis,VAPP）病例的风险。VAPP病例是一种罕见的与口服脊灰减毒活疫苗（Oral Poliomyelitis Attenuated Live Vaccine,OPV）相关的疾病。

关键词： 脊髓灰质炎   分子流行病学   基因突变  

摘要： 脊髓灰质炎（脊灰）是由脊灰病毒引起的以肢体麻痹为主要临床表现的急性肠道传染病。自1988年世界卫生组织（WHO）提出在全球范围内消灭脊灰的目标后,世界各国大力开展口服脊灰减毒活疫苗（OPV）的免疫，脊灰的发病率明显下降。目前本病的流行国家已由1988年的125个降至2008年的4个。

关键词： 接种疫苗   免疫接种   流脑疫苗   麻疹疫苗   脊髓灰质炎疫苗   预防接种   卡介苗   不良反应   乙脑疫苗   传染病  

摘要： 现在绝大部分父母已经知道了按时给宝宝接种的重要性,不过由于疫苗种类多,加上接种时间、禁忌症及副作用各不相同,常让人大伤脑筋。为此,我们特地采访了专家,请他来谈一谈关于宝宝免疫接种的方方面面。

关键词： 脊髓灰质炎灭活疫苗   灭活验证   链特异性RT-PCR  

摘要： 运用链特异性逆转录聚合酶链式反应法(RT-PCR)建立了一种快速、灵敏、特异的脊髓灰质炎灭活疫苗(IPV)的灭活验证体系.以Sabin株脊髓灰质炎病毒悬液作为阳性对照,对脊髓灰质炎灭活疫苗进行检测.结果表明,链特异性RT-PCR法对具有活性的脊髓灰质炎病毒检测为阳性,而对脊髓灰质炎灭活疫苗的检测结果为阴性.链特异性RT-PCR法可作为一种简便、快速、灵敏的脊髓灰质炎灭活疫苗灭活验证方法,大大缩短了检测周期,在脊髓灰质炎灭活疫苗灭活验证的常规检测中具有较好的实际应用价值.

关键词： 脊髓灰质炎   疫苗   口服  

摘要： 目的探讨脊髓灰质炎减毒活疫苗口服方法的临床路径。方法选取2010年1月1日～2010年4月30日在我院预防接种门诊口服脊髓灰质炎疫苗无服苗禁忌的2～4个月正常婴儿1752例,以接种单双日分成对照组和实验组。分别将疫苗配成糖糊或糖粉喂服,观察喂服成功率及省时率。结果两组比较喂服成功率均无显著差异(P>0.05),比较喂服省时率有显著差异(P<0.05)。结论实验组的喂服方法可减少操作环节、省时、喂服成功率也高,可作为脊髓灰质炎减毒活疫苗口服方法的临床路径。

关键词： Gap Junctions   Cells   Sindbis Virus   Poliovirus   Neighbor   Bystander Effect   cells   Connexin 43   cell permeabilization  

摘要： P>Poliovirus 2B protein is a well-known viroporin implicated in plasma membrane permeabilization to ions and low-molecular-weight compounds during infection. Translation in mammalian cells expressing 2B protein is inhibited by hygromycin B (HB) but remains unaffected in mock cells, which are not permeable to the inhibitor. Here we describe a previously unreported bystander effect in which healthy baby hamster kidney (BHK) cells become sensitive to HB when co-cultured with a low proportion of cells expressing poliovirus 2B. Viroporins E from mouse hepatitis virus, 6K from Sindbis virus and NS4A protein from hepatitis C virus were also able to permeabilize neighbouring cells to different extents. Expression of 2B induced permeabilization of neighbouring cell lines other than BHK. We found that gap junctions are responsible mediating the observed bystander permeabilization. Gap junctional communication was confirmed in 2B-expressing co-cultures by fluorescent dye transfer. Moreover, the presence of connexin 43 was confirmed in both mock and 2B-transfected cells. Finally, inhibition of HB entry to neighbouring cells was observed with 18 alpha-glycyrrhethinic acid, an inhibitor of gap junctions. Taken together, these findings support a mechanism involving gap junctional intercellular communication in the bystander permeabilization effect observed in healthy cells co-cultured with poliovirus 2B-expressing cells.

关键词： Anti-poliovirus compound   Poliovirus   Antiviral   VHH   Nanobody  

摘要： VHHs or Nanobodies (R) are single-domain antigen-binding fragments derived from heavy chain antibodies found in camelids. It has already been shown that complex protein mixtures and even whole organisms elicit good immune responses in camelids;therefore we hypothesized that VHHs selected from a dromedary immunized with poliovirus type 1 might inhibit the in vitro replication of poliovirus through binding to essential biological sites on the viral capsid. In this study, we aimed to determine whether VHHs inhibit wild-type and vaccine strains of poliovirus type 1. Interestingly, VHHs showed a potent antipolio activity with EC50 values in the low nanomolar range. Moreover, these antibody fragments completely blocked viral multiplication at higher concentrations. Remarkably, no (immune) escape variants against some of these VHHs could be generated. In conclusion, VHHs fulfil several in vitro requirements to be assigned as potential antiviral compounds for further development of an anti-poliovirus drugs. (C) 2010 Elsevier B.V. All rights reserved.

关键词： viruses   vaccines   commentary  

摘要： The Salk inactivated poliovirus vaccine is one of the most rapid examples of bench-to-bedside translation in medicine. In the span of 6 years, the key basic lab discoveries facilitating the development of the vaccine were made, optimization and safety testing was completed in both animals and human volunteers, the largest clinical trial in history of 1.8 million children was conducted, and the results were released to an eagerly awaiting public. Such examples of rapid translation cannot only offer clues to what factors can successfully drive and accelerate the translational process but also what mistakes can occur (and thus should be avoided) during such a swift process. In this commentary, we explore the translational path of the Salk polio vaccine from the key basic science discoveries to the 1954 Field Trials and delve into the scientific and sociopolitical factors that aided in its rapid development. Moreover, we look at the Cutter and Wyeth incidents after the vaccine's approval and the errors that led to them. Clin Trans Sci 2010;Volume 3: 182-185

关键词： Uridylylation   Post-translational modification   Picornaviruses   Disordered structures   Enteroviruses   Polymerase priming mechanism   RNA editing   Antiviral compounds   Flexibility  

摘要： Picornaviruses have a 22-24 amino acid peptide, VPg, bound covalently at the 5' end of their RNA, that is essential for replication. VPgs are uridylylated at a conserved tyrosine to form VPgpU, the primer of RNA synthesis by the viral polymerase. This first complete structure for any uridylylated VPg, of poliovirus type 1 (PV1)-VPgpU, shows that conserved amino acids in VPg stabilize the bound UMP, with the uridine atoms involved in base pairing and chain elongation projected outward. Comparing this structure to PV1-VPg and partial structures of VPg/VPgpU from other picornaviruses suggests that enteroviral polymerases require a more stable VPg structure than does the distantly related aphthovirus, foot and mouth disease virus (FMDV). The glutamine residue at the C-terminus of PV1-VPgpU lies in back of the uridine base and may stabilize its position during chain elongation and/or contribute to base specificity. Under in vivo-like conditions with the authentic cre(2C) hairpin RNA and Mg2+, 5-methylUTP cannot compete with UTP for VPg uridylyation in an in vitro uridylyation assay, but both nucleotides are equally incorporated by PV1-polymerase with Mn2+ and a poly-A RNA template. This indicates the 5 position is recognized under in vivo conditions. The compact VPgpU structure docks within the active site cavity of the PV-polymerase, close to the position seen for the fragment of FMDV-VPgpU with its polymerase. This structure could aid in design of novel enterovirus inhibitors, and stabilization upon uridylylation may also be pertinent for post-translational uridylylation reactions that underlie other biological processes. (C) 2010 Elsevier Inc. All rights reserved.

关键词： Poliovirus   Oral poliovirus vaccine   Recombination   Chimeric VP1  

摘要： Five oral poliovirus vaccine (OPV) strains carrying an intertypic PV3/PV2 recombination in VP1 capsid protein were isolated during poliovirus surveillance. These five PV3 strains had altogether four diverse recombination crossover points near the 3' end of the VP1 coding region. The complete antigenic site Ilia was replaced by PV2-specific amino acids in four of the studied PV3 strains. Low overall number of nucleotide substitutions in VP1 indicated that the predicted replication time, "age", of the PV3 strains was short, 6 months or less. The nucleotide 472-T in the 5' non-coding region, associated to the attenuated phenotype of PV3/Sabin, was reverted to wild-type C in all studied PV3/PV2 recombinant strains. Three of the PV3 strains had at least a tripartite genome deduced from the partial 3D polymerase-coding region sequences. Our results suggest that there exists a PV3/PV2 recombination hot-spot site in the 3' partial region of the VP1 capsid protein and that the recombination may occur within weeks or a few months after the administration of OPV. (C) 2010 Elsevier B.V. All rights reserved.