摘要： What is already known about this topic? Vaccine-derived polioviruses (VDPVs) can circulate in settings of low population immunity or during outbreaks. What is added by this report? After the 2016 synchronized switch from trivalent oral poliovirus vaccine (OPV) (types 1, 2, and 3) to bivalent OPV (types 1 and 3), transmission of type 2 circulating VDPVs (cVDPVs) was detected in countries with subpopulations of children who missed immunization to type 2 poliovirus before the switch. Types 1 and 3 cVDPVs were identified in Papua New Guinea and Somalia, respectively. What are the implications for public health practice? All countries must maintain high population immunity to polio. Cessation of all OPV use after certification of polio eradication will eliminate the risk for VDPV emergence.

关键词： poliovirus   eukaryotic translation initiation factor 4G (eIF4G)   eukaryotic initiation factor 4A (eIF4A)   RNA-binding protein   eukaryotic translation initiation   plus-stranded RNA virus   internal ribosome entry site (IRES)   vaccine   virulence  

摘要： Recruitment of poliovirus (PV) RNA to the human ribosome requires the coordinated interaction of the viral internal ribosome entry site (IRES) and several host cellular initiation factors and IRES trans-acting factors (ITAFs). Attenuated PV Sabin strains contain point mutations in the PV IRES domain V (dV) that inhibit viral translation. Remarkably, attenuation is most apparent in cells of the central nervous system, but the molecular basis to explain this is poorly understood. The dV contains binding sites for eukaryotic initiation factor 4G (eIF4G) and polypyrimidine tract-binding protein (PTB). Impaired binding of these proteins to the mutant IRESs has been observed, but these effects have not been quantitated. We used a fluorescence anisotropy assay to reveal that the Sabin mutants reduce the equilibrium dissociation constants of eIF4G and PTB to the PV IRES by up to 6-fold. Using the most inhibitory Sabin 3 mutant, we used a real-time fluorescence helicase assay to show that the apparent affinity of an active eIF4G/4A/4B helicase complex for the IRES is reduced by 2.5-fold. The Sabin 3 mutant did not alter the maximum rate of eIF4A-dependent helicase activity, suggesting that this mutant primarily reduces the affinity, rather than activity, of the unwinding complex. To confirm this affinity model of attenuation, we show that eIF4G overexpression in HeLa cells overcomes the attenuation of a Sabin 3 mutant PV-luciferase replicon. Our study provides a quantitative framework for understanding the mechanism of PV Sabin attenuation and provides an explanation for the previously observed cell type-specific translational attenuation.

关键词： 无细胞百白破-Sabin株脊髓灰质炎联合疫苗   小鼠   免疫原性  

摘要： 目的观察候选无细胞百白破-Sabin株灭活脊髓灰质炎联合疫苗（DTaP-sIPV）在小鼠中的免疫原性,为疫苗临床前研究提供依据。方法将候选疫苗分别稀释成5倍、10倍、20倍三组,以相应稀释的无细胞百白破-灭活脊髓灰质炎-b型流感嗜血杆菌联合疫苗（DTaP-IPV/Hib）、无细胞百白破联合疫苗（DTaP）为对照组,每组按0、4、8周3剂免疫程序免疫NIH小鼠（10只/组）,检测各组小鼠每剂免疫后28d的血清百白破组分抗体水平。结果候选疫苗三个组完成3剂次免疫后PT抗体的几何平均浓度（GMC）（IU/mL）分别为2 157.29、2 142.51、2 135.17;FHA抗体GMC分别为10 098.30、10 068.33、9 143.30;PRN抗体GMC分别为1 683.86、1 130.29、193.00;DT抗体几何平均滴度（GMT）（1∶）分别为23.48、22.44、22.44;TT抗体GMT分别为22.31、21.24、21.34。候选疫苗三个组PT、FHA、DT、TT抗体水平均高于两种疫苗对照组或者与其无显著性差异,但PRN抗体水平低于DTaP对照组。结论候选疫苗免疫小鼠具有良好的免疫原性。

关键词： 疫苗高变异脊髓灰质炎病毒   强化免疫  

摘要： 目的分析西藏自治区昌都市1起疫苗高变异脊髓灰质炎（脊灰）病毒（Vaccine high-mutant poliovirus, VHPV）事件,评价应急处置效果。方法对事件涉及的急性弛缓性麻痹（Acute flaccid paralysis, AFP）病例和接触者开展流行病学调查、粪便标本脊灰病毒分离与型内鉴定,对当地县2月龄-5岁儿童开展两轮口服脊灰减毒活疫苗（Oral poliomyelitis attenuated live vaccine, OPV）强化免疫,采用描述性方法分析。结果从1例AFP病例中分离到Ⅲ型脊灰病毒疫苗株（VP1区序列有4个核苷酸变异）,从病例的5名接触者中分离到Ⅰ型VHPV（6个变异）和Ⅲ型VHPV（6-7个变异）。该AFP病例所在乡〈15岁儿童中未发现其他AFP病例,〈5岁儿童中84.4%（146/173）无预防接种记录。当地县实施适龄儿童OPV强化免疫后,昌都市未再发现类似病例及VHPV。结论本次事件经研判为1起多个来源的VHPV同时存在的VHPV事件,脊灰疫苗接种率低是其发生的根本原因,采取OPV应急强化免疫等应急措施及时阻断了可能的VHPV传播。

关键词： 健康人群   免疫水平   免疫成功率   监测  

摘要： 目的了解湘西少数民族地区健康人群脊髓灰质炎(poliomyelitis,以下简称脊灰)免疫水平及1岁内儿童完成脊灰疫苗基础免疫后的免疫效果,为制定脊灰免疫策略提供科学依据。方法随机抽取湘西土家族苗族自治州345名健康人群调查脊髓灰质炎免疫水平,同时选择50名1岁内完成脊灰疫苗基础免疫1个月后的婴幼儿调查免疫成功率,采用微细胞中和试验检测脊灰中和抗体水平。结果 1岁内婴幼儿脊灰I型和III型中和抗体阳性率均为100%,I型和III型抗体几何平均滴度(GMT)分别为1∶916.51和1∶724.09。健康人群中脊灰I型和III型中和抗体阳性率分别为92.26%和97.39%,脊灰I型和III型GMT分别为1∶174.03和1∶95.84;同年龄组中I型GMT均高于III型,0～<3岁组I型和III型GMT最高,各型GMT随着年龄的增长均呈现下降趋势。结论湘西土家族苗族自治州针对脊灰疫苗冷链运转情况好,疫苗接种质量与效果好,脊灰疫苗接种免疫成功率高,健康人群免疫状况良好,已形成牢固的免疫屏障,能有效地控制和阻断脊灰野病毒的传播。

关键词： 二价脊髓灰质炎疫苗   损耗系数   影响因素   疫苗接种   免疫规划  

摘要： 目的分析影响二价脊髓灰质炎疫苗(bOPV)损耗系数的相关因素,为降低bOPV损耗、提高使用效率提供参考依据。方法通过福建省免疫规划信息管理系统查询,福建省共1 046家接种门诊,随机抽取68家接种门诊进行问卷调查;查询九个设区市bOPV使用数和接种数。结果福建省共使用bOPV1 602 980人份,共接种1 125 217人次,平均损耗系数1.43,68家接种门诊平均损耗系数1.42,与福建省平均相比差异无统计学意义(χ~2=1.80,P>0.05)。单因素非条件logistic回归分析显示,乡镇接种门诊较城区接种门诊bOPV损耗系数较大(OR=15.17,P<0.05);接种频次≥3次/周者较接种频率<3次/周的损耗系数小(OR=0.07,P<0.05);接种人员>2人者较接种人员≤2人的损耗系数小(OR=0.01,P<0.05);服务半径≤10km者较服务半径>10km的损耗系数小(OR=0.18,P<0.05)。多因素非条件logistic回归分析显示,接种人员>2人是损耗系数的保护因素(OR=0.01,P<0.05)。分层分析显示,无论服务半径或接种频次,乡镇接种门诊bOPV损耗都高于城区接种门诊。结论要提高bOPV使用率、降低损耗系数,需因地制宜针对城区和乡镇制定对策,合理设置接种门诊,科学安排接种服务周期。

关键词： 急性弛缓性麻痹   Ⅰ型Ⅲ型脊髓灰质炎减毒活疫苗   疫苗免疫程序转换   监测   流行特征  

摘要： 目的了解河北省脊髓灰质炎(脊灰)疫苗免疫程序转换对15岁以下儿童急性弛缓性麻痹(AFP)病例流行特征的影响,为制定科学的防控措施提供依据。方法对河北省脊灰疫苗免疫程序转换前(2015年5月至2016年4月)和转换后(2016年5月至2017年4月)AFP监测系统报告病例进行描述性分析,使用SPSS 21.0软件对数据进行统计检验,率和构成比的比较采用χ2检验和Fisher′s确切概率法。结果脊灰疫苗免疫程序转换前,河北省报告AFP 312例,转换后报告361例,报告发病率分别为2.38/10万和2.58/10万。AFP病例均在夏秋季高发,男性高于女性,集中在0～4岁组;疾病谱均以吉兰–巴雷综合征(又名"格林巴利综合征")为主,但手足口病及脊髓炎病例增多;残留麻痹率分别为11.86%、17.45%;脊灰病毒阳性分离率分别为2.56%、1.66%,优势毒株分别为Ⅰ、Ⅲ型;非脊灰肠道病毒分离率分别为19.23%、12.74%。结论脊灰疫苗免疫程序转换前后,河北省AFP病例的发病率、季节、地区及人群分布均未发生明显改变;疾病谱构成发生变化,残留麻痹增多,非脊灰肠道病毒分离率下降,脊灰病毒优势株由Ⅲ型取代Ⅰ型。

关键词： 表没食子儿茶素没食子酸酯   酒精   脊髓灰质炎病毒   手消毒剂  

摘要： 目的检测含表没食子儿茶素没食子酸酯(EGCG)手消毒剂对脊髓灰质炎1型疫苗株(PV1)的杀灭力,研究能够有效杀灭无囊膜病毒的新型手消毒剂。方法参照2002年版《消毒技术规范》,采用悬液法和载体法检测液体型和凝胶型含EGCG酒精手消毒剂对PV1的杀灭效果,并以含酒精和含碘手消毒剂为平行对照。结果两种剂型的含EGCG手消毒剂分别在与滴度为8.15 Log TCID50的PV1病毒孵育30 s后,PV1滴度降至1.5 Log TCID50和2.17 Log TCID50。对消毒剂进行除药操作后,经消毒剂处理过的PV1依然处于失活状态。含酒精与含碘手消毒剂处理30 s后PV1感染力分别为5.27 Log TCID50和4.87 Log TCID50,对病毒的杀灭效果均未达到《消毒技术规范》要求。结论含EGCG酒精消毒剂对PV1的杀灭效果不可逆,脂溶性EGCG可增强酒精手消毒剂对无囊膜病毒的杀灭效果。

关键词： 脊髓灰质炎   小儿麻痹症   顾方舟   计划免疫   苏联   糖丸   疫苗  

摘要： 20世纪50年代,小儿麻痹症是困扰世界的难题,在中国也流行猖獗。顾方舟等中国医学家走出国门去学习,在艰苦的环境中坚持科研和生产试验,制定出适合中国的技术路线和免疫策略,让无数中国儿童因为吃了糖丸疫苗远离小儿麻痹症。2000年,经世界卫生组织确认,中国成为元脊髓灰质炎国家。

关键词： cancer   immunotherapy   innate immunity   MDA5   oncolytic virus   poliovirus   type I interferon   encephalomyocarditis virus  

摘要： We are pursuing cancer immunotherapy with a neuro-attenuated recombinant poliovirus, PVSRIPO. PVSRIPO is the live attenuated type 1 (Sabin) poliovirus vaccine carrying a heterologous internal ribosomal entry site (IRES) of human rhinovirus type 2 (HRV2). Intratumoral infusion of PVSRIPO is showing promise in the therapy of recurrent WHO grade IV malignant glioma (glioblastoma), a notoriously treatment-refractory cancer with dismal prognosis. PVSRIPO exhibits profound cytotoxicity in infected neoplastic cells expressing the poliovirus receptor CD155. In addition, it elicits intriguing persistent translation and replication, giving rise to sustained type I interferon (IFN)-dominant proinflammatory stimulation of antigen-presenting cells. A key determinant of the inflammatory footprint generated by neoplastic cell infection and its role in shaping the adaptive response after PVSRIPO tumor infection is the virus's inherent relationship to the host's innate antiviral response. In this report, we define subversion of innate host immunity by PVSRIPO, enabling productive viral translation and cytopathogenicity with extremely low multiplicities of infection in the presence of an active innate antiviral IFN response. IMPORTANCE Engaging innate antiviral responses is considered key for instigating tumor-antigen-specific antitumor immunity with cancer immunotherapy approaches. However, they are a double-edged sword for attempts to enlist viruses in such approaches. In addition to their role in the transition from innate to adaptive immunity, innate antiviral IFN responses may intercept the viral life cycle in cancerous cells, prevent viral cytopathogenicity, and restrict viral spread. This has been shown to reduce overall antitumor efficacy of several proposed oncolytic virus prototypes, presumably by limiting direct cell killing and the ensuing inflammatory profile within the infected tumor. In this report, we outline how an unusual recalcitrance of polioviruses toward innate