关键词： 小儿病毒性心肌炎   脊髓灰质炎病毒   柯萨奇病毒   副流感病毒   治疗   诊断   单纯疱疹病毒   病毒感染  

摘要： 病毒性心肌炎是指由嗜心肌病毒感染引起心肌及其间质的炎性损伤,可导致心功能障碍和（或）心律失常,好发于儿童和40岁以下的成年人。1病因病毒感染为本病的直接原因。国内外学者通过研究证实可引起心肌炎的病毒有30余种,其中常见的有柯萨奇病毒、埃可病毒、脊髓灰质炎病毒、腺病毒、流感及副流感病毒、麻疹病毒、单纯疱疹病毒等,以柯萨奇病毒最为常见,约占50%,且可导致一定范围内的流行。

关键词： 脊髓灰质炎病毒   滴度   中和抗体   血清  

摘要： 目的比较6种不同血清对Ⅱ型脊髓灰质炎病毒感染性滴度(CCID50)检测结果的影响。方法分别采用6种未处理血清和6种预处理血清组(免疫吸附法)进行Ⅱ型脊髓灰质炎病毒感染性滴度检测(微细胞病变法),检测了不同组血清中Ⅱ型脊髓灰质炎病毒中和抗体滴度,并使用处理血清组进行促细胞生长试验。最后分析不同血清对感染性滴度的影响。结果6种未处理血清组病毒感染性滴度检测结果差异有统计学意义(P<0.01),6种处理血清组病毒感染性滴度差异无统计学意义(P>0.05)。未处理组2号血清的中和抗体滴度为1∶4,6号血清的中和抗体滴度为1∶8,其余各组血清的中和抗体滴度均<1∶4。6种处理血清组的中和抗体滴度均为1∶2。血清促细胞生长试验显示6种处理组血清细胞生长趋势正常。结论Ⅱ型脊髓灰质炎病毒感染性滴度检测前使用免疫吸附对血清进行预处理,可降低血清中存在的中和抗体对检测的影响,为比较不同实验室数据提供可能。

关键词： poliovirus 2A protease (PV2Apr degrees)   docking   single-nucleotide polymorphisms (SNPs)   non-synonymous SNPs (nsSNPs)   computational analysis   drug binding sites   stability changes  

摘要： Polio viral proteinase 2A performs several essential functions in genome replication. Its inhibition prevents viral replication, thus making it an excellent substrate for drug development. In this study, the three-dimensional structure of 2A protease was determined and optimized by homology modelling. To predict the molecular basis of the interaction of small molecular agonists, docking simulations were performed on a structurally diverse dataset of poliovirus 2A protease (PV2A(pr)degrees) inhibitors. Docking results were employed to identify high risk missense mutations that are highly damaging to the structure, as well as the function, of the protease. Intrinsic disorder regions (IDRs), drug binding sites (DBS), and protein stability changes upon mutations were also identified among them. Our results demonstrated dominant roles for Lys 15, His 20, Cys 55, Cys 57, Cys 64, Asp 108, Cys 109 and Gly 110, indicating the presence of various important drug binding sites of the protein. Upon subjecting these sites to single-nucleotide polymorphism (SNP) analysis, we observed that out of 155 high risk SNPs, 139 residues decrease the protein stability. We conclude that these missense mutations can affect the functionality of the 2A protease, and that identified protein binding sites can be directed for the attachment and inhibition of the target proteins.

关键词： poliovirus   vaccine-derived poliovirus   antigenic evolution   vaccines  

摘要： We followed the dynamics of capsid amino acid replacement among 403 Nigerian outbreak isolates of type 2 circulating vaccine-derived poliovirus (cVDPV2) from 2005 through 2011. Four different functional domains were analyzed: (i) neutralizing antigenic (NAg) sites, (ii) residues binding the poliovirus receptor (PVR), (iii) VP1 residues 1 to 32, and (iv) the capsid structural core. Amino acid replacements mapped to 37 of 43 positions across all 4 NAg sites;the most variable and polymorphic residues were in NAg sites 2 and 3b. The most divergent of the 120 NAg variants had no more than 5 replacements in all NAg sites and were still neutralized at titers similar to those of Sabin 2. PVR-binding residues were less variable (25 different variants;0 to 2 replacements per isolate;30/44 invariant positions), with the most variable residues also forming parts of NAg sites 2 and 3a. Residues 1 to 32 of VP1 were highly variable (133 different variants;0 to 6 replacements per isolate;5/32 invariant positions), with residues 1 to 18 predicted to form a well-conserved amphipathic helix. Replacement events were dated by mapping them onto the branches of time-scaled phylogenies. Rates of amino acid replacement varied widely across positions and followed no simple substitution model. Replacements in the structural core were the most conservative and were fixed at an overall rate similar to 20-fold lower than the rates for the NAg sites and VP1 1 to 32 and similar to 5-fold lower than the rate for the PVR-binding sites. Only VP1 143-Ile, a non-NAg site surface residue and known attenuation site, appeared to be under strong negative selection.

关键词： Oral poliovirus vaccine   Freeze damage   Antigenicity   Vaccine cold chain   Polio eradication   D-antigen  

摘要： According to manufacturers, inactivated poliovirus vaccines (IPVs) are freeze sensitive and require storage between 2 degrees C and 8 degrees C, whereas oral poliovirus vaccine requires storage at -20 degrees C. Introducing IPV into ongoing immunization services might result in accidental exposure to freezing temperatures and potential loss of vaccine potency. To better understand the effect of freezing IPVs, samples of single-dose vaccine vials from Statens Serum Institut (VeroPol) and multi-dose vaccine vials from Sanofi Pasteur (IPOL) were exposed to freezing temperatures mimicking what a vaccine vial might encounter in the field. D-antigen content was measured to determine the in vitro potency by ELISA. Immunogenicity testing was conducted for a subset of exposed IPVs using the rat model. Freezing VeroPol had no detectable effect on in vitro potency (D-antigen content) in all exposures tested. Freezing of the IPOL vaccine for 7 days at -20 degrees C showed statistically significant decreases in D-antigen content by ELISA in poliovirus type 1 (p < 0.0001) and type 3 (p = 0.048). Reduction of poliovirus type 2 potency also approached significance (p = 0.062). The observed loss in D-antigen content did not affect immunogenicity in the rat model. Further work is required to determine the significance of the loss observed and the implications for vaccine handling policies and practices.

关键词： Vaccine-derived poliovirus   Uganda   Poliovirus   Immunization  

摘要： Background: The Oral Polio Vaccine (OPV or Sabin) is genetically unstable and may mutate to form vaccinederived polioviruses (VDPVs). Methods: In 2014, two VDPVs type 2 were identified during routine surveillance of acute flaccid paralysis (AFP) cases. Consequently, a retrospective VDPV survey was conducted to ensure that there was no circulating VDPV in the country. All Sabin poliovirus isolates identified in Uganda 6 months before and 6 months after were rescreened;Sabin 1 and 3 polioviruses were re-screened for Sabin 2 and Sabin 2 polioviruses were re-screened for VDPVs type 2. The Poliovirus rRT-PCR ITD/VDPV 4.0 assay and sequencing were used respectively. Results: The first two VDPVs type2 were identified in Eastern Uganda and the third was identified during the survey from South-western Uganda. These regions had low OPV coverage and poor AFP surveillance indicators. Conclusion: The retrospective VDPV survey was a useful strategy to screen for VDPVs more exhaustively. Supplementary surveillance methods need to be encouraged.

关键词： Preschool booster   dTap-IPV   RCT   Child   UK  

摘要： Aim: To evaluate the immunogenicity and safety of a reduced antigen diphtheria-tetanus-acellular pertussis-inactivated poliovirus (dTap-IPVB) vaccine (Boostrix-IPV, GSK) as a pre-school booster in 3-4 year old children as compared to dTap-IPVR (Repevax, Sanofi Pasteur), when co-administered with mumps-measles-rubella vaccine (MMRV). Methods: This phase III, open label, randomised study was conducted in the UK between April 2011 and April 2012. Children due their pre-school dTap-IPV booster vaccination were randomised 2:1 to receive one of two different dTap-IPV vaccines (dTap-IPVB or dTap-IPVR) with blood sample for immunogenicity assessment just prior and one month after vaccination. Immune responses to diphtheria, tetanus and polio antigens were compared between the study vaccines (inferential comparison). In the absence of an accepted pertussis correlate of protection, the immunogenicity of dTap-IPVB vaccine against pertussis was compared with historical pertussis efficacy data (inferential comparison). Safety and reactogenicity of both study vaccines were evaluated. Results: 387 children were randomised and 385 vaccinated: 255 in the dTap-IPVB group and 130 in the dTap-IPVB group. Prior to vaccination, >= 76.8% of children had anti-diphtheria and >= 65.5% had anti tetanus titres above the protection threshold;for pertussis, the pre-vaccination seropositivity rate ranged between 18.1 and 70.6%. Both vaccines were immunogenic with 99.2-100% of children achieving titres above the pre-specified seroprotection/seropositivity thresholds. One serious adverse event not considered as causally related to the study vaccination by the study investigator was reported in the dTap-IPVB group. Conclusion: Non-inferiority of dTap-IPVB to dTap-IPVB was demonstrated. Both vaccines had a clinically acceptable safety and reactogenicity profile when co-administered with MMRV to children 3-4 years old. (C) 2018 The Author(s). Published by Elsevier Ltd.

关键词： Poliomyelitis   Pakistan   Sewage   Multi-state models   Sensitivity  

摘要： Background: To support poliomyelitis eradication in Pakistan, environmental surveillance (ES) of wastewater has been expanded alongside surveillance for acute flaccid paralysis (AFP). ES is a relatively new method of surveillance, and the population sensitivity of detecting poliovirus within endemic settings requires estimation. Methods: Data for wild serotype 1 poliovirus from AFP and ES from January 2011 to September 2015 from 14 districts in Pakistan were analysed using a multi-state model framework. This framework was used to estimate the sensitivity of poliovirus detection from each surveillance source and parameters such as the duration of infection within a community. Results: The location and timing of poliomyelitis cases showed spatial and temporal variability. The sensitivity of AFP surveillance to detect serotype 1 poliovirus infection in a district and its neighbours per month was on average 30.0% (95% CI 24.8-35.8) and increased with the incidence of poliomyelitis cases. The average population sensitivity of a single environmental sample was 59.4% (95% CI 55.4-63.0), with significant variation in site-specific estimates (median varied from 33.3-79.2%). The combined population sensitivity of environmental and AFP surveillance in a given month was on average 98.1% (95% CI 97.2-98.7), assuming four samples per month for each site. Conclusions: ES can be a highly sensitive supplement to AFP surveillance in areas with converging sewage systems. As ES for poliovirus is expanded, it will be important to identify factors associated with variation in site sensitivity, leading to improved site selection and surveillance system performance.

关键词： Polio   Eradication   Risk management   Oral poliovirus vaccine   Dynamic modeling   Vaccine-derived poliovirus  

摘要： Background: Oral polio vaccine (OPV) containing attenuated serotype 2 polioviruses was globally withdrawn in 2016, and bivalent OPV (bOPV) containing attenuated serotype 1 and 3 polioviruses needs to be withdrawn after the certification of eradication of all wild polioviruses to eliminate future risks from vaccine-derived polioviruses (VDPVs). To minimize risks from VDPVs, the planning and implementation of bOPV withdrawal should build on the experience with withdrawing OPV containing serotype 2 polioviruses while taking into account similarities and differences between the three poliovirus serotypes. Methods: We explored the risks from (i) a failure to synchronize OPV cessation and (ii) unauthorized post-cessation OPV use for serotypes 1 and 3 in the context of globally-coordinated future bOPV cessation and compared the results to similar analyses for serotype 2 OPV cessation. Results: While the risks associated with a failure to synchronize cessation and unauthorized post-cessation OPV use appear to be substantially lower for serotype 3 polioviruses than for serotype 2 polioviruses, the risks for serotype 1 appear similar to those for serotype 2. Increasing population immunity to serotype 1 and 3 poliovirus transmission using pre-cessation bOPV supplemental immunization activities and inactivated poliovirus vaccine in routine immunization reduces the risks of circulating VDPVs associated with non-synchronized cessation or unauthorized OPV use. Conclusions: The Global Polio Eradication Initiative should synchronize global bOPV cessation during a similar window of time as occurred for the global cessation of OPV containing serotype 2 polioviruses and should rigorously verify the absence of bOPV in immunization systems after its cessation.

关键词： 响应曲面法   层析工艺优化   Sabin株脊髓灰质炎疫苗  

摘要： 采用响应曲面法(RSM),对Sabin株脊髓灰质炎(Vero细胞)灭活疫苗离子交换层析工艺进行研究。首先确定离子交换平衡缓冲液的盐浓度、pH和上样流速为三个关键工艺参数,然后利用Design expert软件,以层析液D抗原含量和DNA残留量为响应,引入模型,对已筛选出的三个关键工艺参数进行最佳水平的探究和优化,最终得到因素最佳水平组合为:0.02MPBS(0.32MNaCl)、pH6.84的平衡缓冲液,上样流速24cm/h。能够得到的抗原回收率为94.8%,DNA残留量为61pg/ml。中试放大连续三批验证得到的抗原回收率均为90%以上(平均95%),DNA含量平均为55pg/ml。应用响应曲面法对Sabin株脊髓灰质炎(Vero细胞)I型层析工艺研究得到的结果准确可靠,具有实用价值。