关键词： Poliovirus   Inactivated vaccine   Sabin   Infnats   Toddlers  

摘要： Background: To increase the global supply of affordable IPV vaccine, preferably using Sabin viruses to comply with GAPIII requirements, Takeda has assessed three dosages of a stand-alone sIPV. Methods: In this phase I/II study two cohorts of 40 adults and 60 toddlers, respectively, were initially assessed for safety after receiving high-dosage sIPV compared with placebo (adults) or Salk IPV (toddlers). A cohort of 240 infants was then enrolled and randomized (1:1:1:1) to receive low-, medium- or high-dosage sIPV, or a reference Salk IPV in a three-dose primary schedule at 6, 10 and 14 weeks of age. Parents completed safety diaries for 4 weeks after each dose, and immunogenicity was measured as neutralization antibody titers at baseline and four weeks after vaccination. Results: All vaccinations were generally well-tolerated and sIPV had a comparable safety profile to the control arm in adults or the reference Salk IPV vaccine in toddlers and infants. Infants displayed dosage-dependent immune responses to sIPV when assayed using Sabin strains, which were equivalent to the reference IPV in the high-dosage sIPV group for serotypes 1 and 2, but not for Sabin and Salk serotype 3. Seroconversion rates (SCR) of the low- and medium-dosage groups were significantly lower than the Salk IPV group for both Sabin and Salk serotypes 1 and type 2 (p < 0.05), with no significant differences for Salk or Sabin serotypes 3. Responses to sIPV, particularly to Sabin types 1 and 2, were higher in initially seronegative infants, indicating possible interference by maternally-derived antibodies. Conclusions: A novel stand-alone Sabin-based IPV vaccine was well tolerated with an acceptable safety profile, but less immunogenic than reference Salk IPV at 6, 10 and 14 weeks of age for Salk serotypes 1 and 2, with apparent interference by maternal antibodies. Additional preclinical assessments will be made before any further clinical development. (C) 2020 Takeda Vaccines Inc. Published by Elsev

关键词： 手足口病   自限性疾病   发病人群   CA16   脊髓灰质炎病毒   常见症状   肠道病毒71型   感染性疾病  

摘要： 手足口病是一种婴幼儿常见的感染性疾病,主要发病人群为5岁以下儿童,常见症状为发热,痛性口腔溃疡,手足、臀部出现疱疹。手足口病可由多种肠道病毒引起,包括肠道病毒71型(EV71 )、柯萨奇A组16型(CA16)、艾柯病毒、脊髓灰质炎病毒等。其中,CA16是引起手足口病的常见病毒,通常导致较轻的自限性疾病,很少出现并发症。

关键词： 脊髓灰质炎   脊髓灰质炎病毒疫苗,口服   疫苗效果   疫苗效价  

摘要： 目的分析脊髓灰质炎(脊灰)疫苗免疫程序策略调整前后北京市2012、2014、2016和2018年脊灰疫苗免疫效果和疫苗效价。方法按照方便抽样的方法,于2012年选择朝阳区和延庆区,2014选择丰台区和大兴区,2016年选择通州区和平谷区,2018年选择东城区和顺义区的预防接种门诊作为监测点,选取在监测点内完成3剂脊灰疫苗基础免疫后4~8周的儿童为监测对象,共292名,其中2012和2014年为策略调整前,免疫程序为3剂3价脊灰病毒减毒活疫苗(tOPV)全程免疫;2016和2018年为策略调整后,免疫程序为1剂脊灰病毒灭活疫苗(IPV)与2剂2价脊灰病毒减毒活疫苗(bOPV)序贯免疫。采集1.0 ml静脉血,检测Ⅰ和Ⅲ型脊灰病毒中和抗体滴度。采用随机数字法,从监测点随机抽取疫苗标本,每年9份(2012年为8份),检测疫苗效价并进行比较。结果292名儿童的年龄[M(P25,P75)]为5(5,6)月龄,男女比为1.04(149/143)。2012、2014、2016和2018年监测对象分别为66、72、68和86名,基础免疫后,除2014年Ⅰ型脊灰病毒中和抗体阳性率为98.61%(71名),其余年份Ⅰ和Ⅲ型均为100%;2016和2018年Ⅰ和Ⅲ型脊灰病毒中和抗体滴度整体高于2012和2014年(P值均<0.001)。2012和2014年tOPV的效价为(6.05±0.15)和(6.16±0.12)lgCCID50/粒,2016和2018年bOPV的效价为(6.88±0.21)和(6.26±0.14)lgCCID50/100μl(P<0.001)。结论北京市脊灰疫苗免疫策略调整前后,tOPV全程免疫和IPV‑bOPV序贯免疫程序的疫苗基础免疫抗体阳性率相当,IPV‑bOPV序贯免疫程序产生的脊灰抗体水平更高,调整后2016年bOPV效价高于调整前tOPV效价,但2018年bOPV效价下降。

关键词： 脊髓灰质炎   减毒活疫苗   序贯程序   基础免疫  

摘要： 目的评价口服脊髓灰质炎(简称脊灰)减毒活疫苗(oral live attenuated poliomyelitis vaccine,OPV)和脊灰灭活疫苗(inactivated poliomyelitis vaccine,IPV)不同序贯程序的基础免疫效果。方法选取上海市浦东新区居住的≥2月龄婴儿为研究对象,分别于2、3、4月龄进行序贯(I-I-O)组、OPV全程(O-O-O)组和IPV全程(I-I-I)组的基础免疫程序的接种,检测免疫前及完成基础免疫后,各组血清中脊灰病毒中和抗体,并计算保护率及几何平均滴度(GMT)。结果各组研究对象体重、性别构成比差异无统计学意义(P>0.05),年龄差异有统计学意义(P<0.05);免疫前,O-O-O组Ⅰ、Ⅲ型脊灰抗体GMT分别为24.14和4.44,抗体保护率分别为30.56%和13.89%;I-I-O组Ⅰ、Ⅲ型抗体GMT分别为11.86和5.91,抗体保护率分别为30.00%和15.71%;I-I-I组Ⅰ、Ⅲ型抗体GMT分别为22.72和16.14,抗体保护率分别为43.06%和31.74%;各组间Ⅰ、Ⅲ型脊灰中和抗体GMT和Ⅰ型保护率差异均无统计学意义(P>0.05),但Ⅲ型脊灰中和抗体保护率差异有统计学意义(P<0.05)。基础免疫后,O-O-O组Ⅰ、Ⅲ型抗体GMT分别为1325.33和946.69,抗体保护率为100%和98.61%;I-I-O组Ⅰ、Ⅲ型抗体GMT分别为1840.91和1858.51,抗体保护率均为100%;I-I-I组Ⅰ、Ⅲ型抗体GMT分别为1085.56和644.86,抗体保护率为100%和98.61%;各组间Ⅰ、Ⅲ型脊灰中和抗体GMT差异均有统计学意义(P<0.001),抗体保护率差异无统计学意义(P>0.05)。结论各种免疫程序均能获得较高的抗体保护率,其中国产IPV与OPV进行序贯接种后,能产生较好的免疫效果,可为受种儿童建立更有效的免疫屏障。

关键词： Coxsackievirus   Poliovirus   Antibiotics   Microbiota  

摘要： Coxsackieviruses primarily infect the gastrointestinal tract of humans, but they can disseminate systemically and cause severe disease. Using antibiotic treatment regimens to deplete intestinal microbes in mice, several groups have shown that bacteria promote oral infection with a variety of enteric viruses. However, it is unknown whether antibiotics have microbiota-independent antiviral effects for enteric viruses or whether antibiotics influence extra-intestinal, systemic infection. Here, we examined the effects of antibiotics on systemic enteric virus infection by performing intraperitoneal injections of either coxsackievirus B3 (CVB3) or poliovirus followed by quantification of viral titers. We found that antibiotic treatment reduced systemic infection for both viruses. Interestingly, antibiotics reduced CVB3 titers in germ-free mice, suggesting that antibiotic treatment alters CVB3 infection through a microbiota-independent mechanism. Overall, these data provide further evidence that antibiotics can have noncanonical effects on viral infection.

关键词： Immunization   Poliomyelitis   Seroprevalence   Lebanon  

摘要： Introduction: Circulation of poliovirus in neighboring countries and mass population movement places Lebanon at risk of polio and other vaccine-preventable disease outbreaks. Determining population immunity levels is essential for guiding program planning and implementation of targeted supplementary immunization activities (SIAs) in governorates and subpopulations with low seroprevalence. Methods: A cross-sectional multi-stage cluster survey was conducted during February-December 2016 in all six governorates of Lebanon adapted from the World Health Organization (WHO) recommended Expanded Progamme on Immunization (EPI) methodology. Sera from selected children aged 12-59 months were tested for poliovirus neutralizing antibodies. Results: Of 2,164 children recruited in this study, 1,893 provided sufficient quantity of serum samples for laboratory testing. Seroprevalence for all three poliovirus serotypes was greater than 90% in all six governorates. Poliovirus vaccine coverage with three or more doses, based on vaccination cards or parental recall, ranged between 54.1% for children aged 36-47 months in the North and 83.5% for children aged 48-59 months in Beirut. Conclusion: Immunity to polioviruses was high in Lebanon in 2016 following a series of supplementary immunization activities. It is essential to continue strategies that increase vaccination coverage in order to sustain the considerably high immunity levels and prevent reintroduction and transmission of poliovirus. Educating caregivers and training health care workers on the standardized usage of home-based vaccination records is needed to guarantee the accuracy of records on children's vaccination status. (C) 2020 Elsevier Ltd. All rights reserved.

关键词： 脊髓灰质炎   单价口服脊髓灰质炎减毒活疫苗   免疫原性   疫苗储备  

摘要： 口服脊灰减毒活疫苗(Oral poliomyelitis attenuated live vaccine,OPV)在全球消灭脊髓灰质炎(脊灰)行动中发挥了重要作用,Ⅱ、Ⅲ型脊灰野病毒(Wild poliovirus,WPV)分别于2015年和2019年在全球宣布被消灭。为了根除WPV病例、疫苗相关麻痹型脊灰和疫苗衍生脊灰病毒(Vaccine-derived poliovirus,VDPV)病例,发展中国家包括中国已停止使用三价OPV,改用脊灰灭活疫苗(Inactivated poliovirus vaccine,IPV)和二价OPV序贯免疫。由于中国仍存在较高的WPV输入和VDPV循环的风险,单价OPV(Monovalent OPV,mOPV)储备对于应对输入性WPV疫情、VDPV循环和迅速提高人群脊灰免疫力具有重要意义。本文综述了mOPV的免疫原性及其在应急补充接种活动中的优势。

关键词： 脊髓灰质炎病毒   脊髓灰质炎Ⅲ型病毒Sabin株   C抗原   D抗原   生物学特性  

摘要： 目的对脊髓灰质炎Ⅲ型病毒Sabin株C抗原和D抗原在形态、感染特性、核酸含量和结构基因核苷酸序列、抗原不同结构蛋白质含量及2种抗原免疫原性等方面的差异进行比较观察,为脊髓灰质炎疫苗的生产评估、检定及进一步在蛋白质翻译后水平研究2种抗原的差异提供依据。方法采用二次氯化铯(CsCl)密度梯度离心的方法分离纯化脊髓灰质炎Ⅲ型病毒Sabin株C、D抗原,对分离的C、D抗原采用微量BCA(bicinchonininc acid)法检测蛋白质浓度,电镜观察病毒形态和纯度,聚丙烯酰胺凝胶电泳(polyacrylamide gel electrophoresis,PAGE)检测病毒不同结构蛋白质组成和含量,逆转录PCR(reverse transcription-PCR,RT-PCR)定量检测2种抗原单位质量携带核酸含量,并测序比较结构基因核苷酸序列差异;以中高剂量的C、D抗原分别免疫Wistar雌性大鼠,观察2种抗原体内诱生中和抗体的能力。结果脊髓灰质炎Ⅲ型病毒Sabin株单位质量D抗原的病毒滴度高于C抗原约4个对数值;单位质量D抗原的核酸含量高于C抗原近64倍,D抗原和C抗原结构基因核苷酸序列无差异;单位质量D抗原VP1蛋白质含量高于C抗原1.67倍;一次免疫后,D抗原诱导的中和抗体是C抗原的10~50倍。结论脊髓灰质炎Ⅲ型病毒Sabin株D抗原比C抗原具有较强的免疫原性,上述研究结果为脊髓灰质炎疫苗C、D抗原的检测、鉴定及进一步的疫苗效力研究和提高疫苗效力提供了实验依据。

关键词： 脊灰病毒   突发公共卫生事件   再接种   常规免疫   OPV   野病毒   三价   疫苗株  

摘要： 2015年,世界卫生组织宣布Ⅱ型脊髓灰质炎(脊灰)野病毒已被消灭。为防止Ⅱ型疫苗衍生脊灰病毒(VDPV2)的发生,自2016年4月起,全球范围内将Ⅱ型脊灰病毒疫苗组分从三价口服脊灰减毒活疫苗(tOPV)中撤出。中国与其他使用tOPV的国家同步撤出了Ⅱ型脊灰病毒疫苗组分,将常规免疫策略改为先接种1剂次三价脊灰灭活疫苗(IPV),然后再接种3剂次含I型和Ⅲ型脊灰病毒疫苗组分的二价口服脊灰减毒活疫苗(bOPV)。在所有国家停用Ⅱ型脊灰病毒疫苗组分后,对新生儿Ⅱ型脊灰病毒的常规免疫保护仅来自三价的IPV。此后,预测会有小范围的VDPV2暴发,并且此类暴发须依靠单价的Ⅱ型脊灰减毒活疫苗进行阻断。无论在任何来源的任何样本中检测到Ⅱ型脊灰病毒,包括Ⅱ型脊灰野病毒(WPV)、VDPV2和Sabin疫苗株,通常都被认为是全球突发公共卫生事件,需要开展紧急调查和应对。

关键词： 脊髓灰质炎疫苗   七五三   儿童节   快餐店   男孩节  

摘要： 瑞典儿童节分为8月7日“男孩节”和12月13日“女孩节”.11月15日是日本的七五三儿童节。这天,3岁、5岁、7岁的小朋友会身穿和服庆祝,还能吃到“千岁糖”.8月15日是巴西儿童节,也是“国防疫日”.政府规定,当天医生要给5岁以下的儿童接种脊髓灰质炎疫苗。