关键词： Oral polio vaccine   Heterologous immunity   Non-specific effect   Bacillus Calmette-Guerin   Infant  

摘要： Background: Vaccines may have non-specific effects. An observational study from Guinea-Bissau suggested that oral polio vaccine at birth (OPV0) provided with Bacillus Calmette-Guerin (BCG) vaccine was associated with down-regulation of the immune response to BCG vaccine 6 weeks later. Based on the previous finding, we wanted to test our a priori hypothesis that OPV would dampen the immune response to BCG, and secondarily to test immune responses to other antigens. Methods: The study was conducted at the Bandim Health Project in Guinea-Bissau in 2009-2010. Infants were randomised to OPV0+BCG versus BCG alone at birth, and subsequently randomised to have a blood sample taken at 2, 4 or 6 weeks post-randomisation. Excreted levels of cytokines (IL-2, IL-5, IL-10, TNF-alpha and IFN-gamma) were measured from whole blood in vitro stimulations with a panel of recall vaccine antigens (BCG, PPD, OPV), mitogen (PHA) or innate agonists (LPS, Pam3cys, PolyI:C). Additionally, we measured the local reaction to BCG, white blood cell distribution, C-reactive protein (CRP) and retinol-binding protein (RBP). Cytokine production was analysed as the prevalence ratios of responders above the median. Results: Blood samples from 430 infants (209 OPV0+BCG;221 BCG alone) were analysed. There were no strong differences in effects 2, 4 and 6 weeks post-randomisation and subsequent analyses were performed on the pooled data. As hypothesised, receiving OPV0+BCG versus BCG alone was associated with significantly lower prevalence of IFN-gamma responses to PPD (prevalence ratio (PR): 0.84 (0.72-0.98)) and reduced IL-5 to PPD (PR: 0.78 (0.64-0.96)). No effects were observed for CPR, RBP, white blood cell distribution, or BCG scar prevalence. Conclusion: The results corroborate that OPV attenuates the immune response to co-administered BCG at birth. (C) 2014 The Authors. Published by Elsevier Ltd.

关键词： 脊髓灰质炎灭活疫苗   脊髓灰质炎减毒活疫苗   免疫活性   序贯程序  

摘要： 目的 评价脊髓灰质炎灭活疫苗（inactived polio vaccine,IPV）与口服脊髓灰质炎减毒活疫苗（oral polio vaccine,OPV）不同序贯免疫程序的基础及加强免疫效果。方法 选择逸2月龄婴儿,分为4组：1剂IPV和2剂OPV序贯（I-O-O组）;2剂IPV和1剂OPV序贯（I-I-O组）;3剂IPV（I-I-I组）;3剂OPV（O-O-O组）,以O-O-O组为对照组,分别于2、3、4月龄各接种1剂,IPV每剂悬液0.5 ml,经大腿前外侧中部肌肉注射,OPV每剂口服1 g糖丸。均采集免疫前、完成基础免疫后1个月、满18月龄后及I-O-O组接种第1剂IPV后1个月、I-I-O组接种第2剂IPV后1个月、I-I-I组加强免疫1剂IPV后1个月受试者的静脉血,分离血清,由北京市CDC脊髓灰质炎实验室采用WHO推荐的微量中和试验方法检测脊髓灰质炎中和抗体水平,计算各组抗体保护率及几何平均滴度（GMT）。结果 各组研究对象的体重、性别构成比差异无统计学意义（P跃0.05）,年龄差异有统计学意义（P约0.05）。免疫前各组脊髓灰质炎Ⅰ、Ⅱ、Ⅲ型中和抗体水平均低于1：8,其中以Ⅲ型最低。完成3剂基础免疫后,I-O-O和I-I-O组Ⅰ、Ⅱ、Ⅲ型中和抗体GMT在889.20-1 193.99之间,I-I-I和O-O-O组在243.22-831.76之间;O-O-O组的Ⅰ型和Ⅲ型抗体保护率均为96.67%,I-O-O组的Ⅲ型为97.18%,其余均为100%。I-O-O组接种第1剂IPV后,Ⅰ、Ⅱ、Ⅲ型中和抗体GMT分别为21.73、39.63和26.49,抗体保护率分别为88.10%、97.62%和84.52%;I-I-O组接种第2剂IPV后,Ⅰ、Ⅱ、Ⅲ型中和抗体GMT分别为234.96、247.74和416.87,抗体保护率均为100%。基础免疫后1年,I-O-O、I-I-O和O-O-O组Ⅰ、Ⅱ、Ⅲ型中和抗体GMT均高于I-I-I组（P约0.05）,抗体保护率均为100%;I-I-I组加强1剂IPV后,Ⅰ、Ⅱ、Ⅲ型中和抗体GMT均为1 819.70,抗体保护率均为100%。结论 序贯接种组抗体较单独接种IPV或OPV组高。基础免疫1年后抗体保护率仍较高,但I-I-I组需1年后加强1剂,以保持较高水平的抗体滴度。

关键词： 肠道病毒   脊髓灰质炎病毒   安徽省阜阳市   脑干脑炎   enterovirus   神经源性肺水肿   疱疹性咽峡炎   病毒基因   抗病毒药物   病毒衣壳蛋白  

摘要： 肠道病毒71型（enterovirus 71,EV71）目前被认为是引起儿童手足口病的主要病原体之一。该病毒可以引起疱疹性咽峡炎、脑干脑炎、神经源性肺水肿等多种疾病,EV71感染引起的手足口病呈周期性暴发与流行,在亚太地区暴发较为严重。我国自2008年5月,安徽省阜阳市暴发了EV71相关性手足口病以来,在此后5年内中国部分地区逐渐呈现增多趋势。

关键词： 疫苗衍生脊髓灰质炎病毒   脊灰减毒活疫苗   世界卫生大会   消灭脊灰   体液免疫   保护作用   志愿者   OPV  

摘要： 1988年,世界卫生大会确立了全球消灭脊髓灰质炎（脊灰）的目标。在消灭脊灰所做的努力中,一个主要工具是口服脊灰减毒活疫苗（Oral Poliomyelitis Attenuated Live Vaccine,OPV）,这种疫苗价格不高,可以由受过培训的志愿者进行喂服。可能需要几剂OPV才能为受种者提供完全免疫,这样能通过持久的体液免疫提供长期的保护作用以预防麻痹型脊灰。

关键词： 疫苗相关麻痹性脊髓灰质炎病例   口服脊髓灰质炎减毒活疫苗   流行病学  

摘要： 目的为了解国内文献报道的疫苗相关麻痹型脊髓灰质炎病例（Vaccine-associated paralytice poliomyelitis,VAPP）发病情况及流行病学特征,探讨VAPP发生的危险因素,为预防接种人员提供接种依据,同时为疑似预防接种异常反应专家组诊断提供参考。方法采用描述流行病学方法对国内文献报道的1980~2012年发生的188例VAPP进行分析。结果发病年龄以≤6月龄为主,占病例总数的66.4%,男女比为3∶1,首次服苗病例数为再次服苗的3.24倍,病毒分型以Ⅱ型为主。结论在我国维持无脊灰阶段,减少VAPP发生成为消灭脊灰的重要内容之一,应引起高度重视。

关键词： 脊髓灰质炎病毒疫苗,口服   脊髓灰质炎病毒疫苗,灭活   世界卫生组织   意见书  

摘要： 此文介绍了脊髓灰质炎病毒的流行病学、目前国际上使用的2种脊髓灰质炎疫苗的安全性、免疫原性和效果以及WHO对脊髓灰质炎疫苗的意见.

关键词： 脊髓灰质炎灭活疫苗   MF59佐剂   细胞因子   细胞免疫  

摘要： 目的分析以MF59为佐剂的脊髓灰质炎灭活疫苗(IPV)免疫恒河猴后诱导的细胞免疫应答。方法将恒河猴分为4组:无佐剂低剂量组(IPVL-PBS组)、低剂量MF59佐剂组(IPVL-MF59组)、无佐剂高剂量组(IPVH-PBS组)和低剂量铝佐剂组(IPVL-AL组)。高剂量组IPV每剂中Ⅰ、Ⅱ、Ⅲ型抗原含量分别为30、32、42 DU,低剂量组IPV每剂中Ⅰ、Ⅱ、Ⅲ型抗原含量分别为3、3.2、4.2 DU,0.5 ml/剂,其中MF59为0.25 ml/剂,氢氧化铝为0.5 mg/剂,均于第1、28、56天经恒河猴后腿肌肉注射,分别于免疫后第28、56、84天采血,分离血清,微量中和试验法检测血清中和抗体效价;分别于免疫后第56和84天,取外周血,分离淋巴细胞,上流式细胞仪检测特异性抗原刺激下的Th1型细胞因子(IL-2、IFNγ、TNF)和Th2型细胞因子(IL-4、IL-5、IL-6)分泌水平,以及CD3+、CD4+、CD8+T淋巴细胞比例的分布情况。结果恒河猴经3次免疫后,IPVL-MF59组血清中和抗体阳转率明显高于其他各组,达75%以上。恒河猴免疫后第56天,IPVL-MF59组IFNγ和TNF分泌水平明显高于IPVL-AL组(P均<0.05),IL-6分泌水平明显高于IPVL-PBS和IPVH-PBS组(P均<0.05);免疫后第84天,各组IL-2、IFNγ、TNF均稳定在同一水平,IL-4、IL-5分泌水平均明显高于第56天(P均<0.05)。免疫后第84天,IPVL-MF59组CD8+T淋巴细胞百分比均明显高于IPVH-PBS和IPVL-PBS组(P均<0.05)。结论 MF59佐剂能增强IPV诱导的TNF和IL-6的分泌水平,增强Th1和Th2类反应。

关键词： FORMALDEHYDE   POLIOMYELITIS vaccines   POLIO   REVERSE transcriptase polymerase chain reaction   THERAPEUTICS   VACCINES  

摘要： Inactivated polio vaccines, which have been used in many countries for more than 50 years, are produced by treating live poliovirus (PV) with formaldehyde. However, the molecular mechanisms underlying virus inactivation are not well understood. Infection by PV is initiated by virus binding to specific cell receptors, which results in viral particles undergoing sequential conformational changes that generate altered structural forms (135S and 80S particles) and leads to virus cell entry. We have analyzed the ability of inactivated PV to bind to the human poliovirus receptor (hPVR) using various techniques such as ultracentrifugation, fluorescence-activated cell sorting flow cytometry and real-time reverse transcription-PCR (RT-PCR). The results showed that although retaining the ability to bind to hPVR, inactivated PV bound less efficiently in comparison to live PV. We also found that inactivated PV showed resistance to structural conversion in vitro, as judged by measuring changes in antigenicity, the ability to bind to hPVR, and viral RNA release at high temperature. Furthermore, viral RNA from inactivated PV was shown to be modified, since cDNA yields obtained by RT-PCR amplification were severely reduced and no infectious virus was recovered after RNA transfection into susceptible cells. IMPORTANCE This study represents a novel insight into the molecular mechanisms responsible for poliovirus inactivation. We show that inactivation with formaldehyde has an effect on early steps of viral replication as it reduces the ability of PV to bind to hPVR, decreases the sensitivity of PV to convert to 135S particles, and abolishes the infectivity of its viral RNA. These changes are likely responsible for the loss of infectivity shown by PV following inactivation. Techniques used in this study represent new approaches for the characterization of inactivated PV products and could be useful in developing improved methods for the production and quality control testing of inacti

关键词： design of experiments   formulation   inactivated polio vaccine   lyophilization  

摘要： Purpose The aim of current study was to develop a dried inactivated polio vaccine (IPV) formulation with minimal loss during the drying process and improved stability when compared with the conventional liquid IPV. Methods Extensive excipient screening was combined with the use of a Design of Experiment (DoE) approach in order to achieve optimal results with high probability. Results Although it was shown earlier that the lyophilization of a trivalent IPV while conserving its antigenicity is challenging, we were able to develop a formulation that showed minimal loss of potency during drying and subsequent storage at higher temperatures. Conclusion This study showed the potential of a highly stable and safe lyophilized polio vaccine, which might be used in developing countries without the need of a cold-chain.

关键词： Poliovirus   Picornavirus   VP1   V-073   Pirodavir   Capsid-binder  

摘要： A novel small molecule, H1PVAT, was identified as a potent and selective inhibitor of the in vitro replication of all three poliovirus serotypes, whereas no activity was observed against other enteroviruses. Time-of-drug-addition studies revealed that the compound interfered with an early stage of virus replication. Four independently-selected H1PVAT-resistant virus variants uniformly carried the single amino acid substitution I194F in the VP1 capsid protein. Poliovirus type 1 strain Sabin, reverse-engineered to contain this substitution, proved to be completely insensitive to the antiviral effect of H1PVAT and was cross-resistant to the capsid-binding inhibitors V-073 and pirodavir. The VP1 I194F mutant had a smaller plaque phenotype than wild-type virus, and the amino acid substitution rendered the virus more susceptible to heat inactivation. Both for the wild-type and VP1 I194F mutant virus, the presence of H1PVAT increased the temperature at which the virus was inactivated, providing evidence that the compound interacts with the viral capsid, and that capsid stabilization and antiviral activity are not necessarily correlated. Molecular modeling suggested that H1PVAT binds with high affinity in the pocket underneath the floor of the canyon that is involved in receptor binding. Introduction of the I194F substitution in the model of VP1 induced a slight concerted rearrangement of the core beta-barrel in this pocket, which disfavors binding of the compound. Taken together, the compound scaffold, to which H1PVAT belongs, may represent another promising class of poliovirus capsid-binding inhibitors next to V-073 and pirodavir. Potent antivirals against poliovirus will be essential in the poliovirus eradication end-game. (C) 2014 Published by Elsevier B.V.