关键词： Reaction products   Phenyls   Photovoltaics   Vaccination   Inhibitors  

摘要： The final stages of polio eradication are proving more difficult than the early phases, and the development of effective drugs and treatments is considered a priority;thus, the research is ongoing. A screening of our in-house chemical library against poliovirus Sabin strains led to the identification of compounds 5 and 6 as hits active at submicromolar concentrations. Derivatives of these compounds were synthesized as a preliminary structure-activity-relationship study. Among them, 7 and 11 were highly active against poliovirus Sabin 1-3. Compound 11 was also very potent against a large panel of wild and vaccine-derived polioviruses. Time-of-addition experiments suggest that 5 and 7 could be active at an early stage of viral replication, whereas 11 was active at same concentration at all stages of viral replication. A ligand-based approach was applied to find the common structural features shared by the new compounds and already-known poliovirus inhibitors.

关键词： Wild polio virus (WPV)   Circulatory vaccine derived polio virus (cVDPV)   Acute flaccid paralysis (AFP)   Vaccine diplomacy   Polio eradication   Health diplomacy   Global health diplomacy (GHD)  

摘要： BackgroundOn April 28, 2014, the World Health Organization (WHO) declared polio a Public Health Emergency of International Concern (PHIC) under the authority of the International Health Regulations. Although polio has been eradicated from nearly every nation on earth, Pakistan is one of three countries where wild polio and vaccine-derived polio strains remain, thwarting global eradication *** eradication progress is complicated by security and conflict issues at the border area between Pakistan and Afghanistan. In addition to security issues,other critical challenges, such as maintaining cold supply chain for vaccines, active and sentinel surveillance, false beliefs about vaccines, distrust of healthcare workers, and accessibility to conflict areas due to terrorist activities, all play a role in the continued persistence of Polio. In response to these challenges, weassess the local and international policy environment and its impact on polio eradication in *** on our analysis of existing barriers and challenges associated with polio eradication in Pakistan, this study discusses why employing vaccine diplomacy represents a key policy and advocacy strategic approach to achieve the overall end game of polio eradication. Specifically, we identify a set of concrete public health, international development, and diplomatic and policy recommendations that can act synergistically under the umbrella of health and vaccine diplomacy to finally put an end to polio.

关键词： Oral polio vaccination   Poliomyelitis   Enteropathogen infection   Home environment  

摘要： Background: Immunization programs have leveraged decades of research to maximize oral polio vaccine (OPV) response. Moving toward global poliovirus eradication, the WHO recommended phased OPV-to-IPV replacement on schedules in 2012. Using the MAL-ED prospective birth cohort data, we evaluated the influence of early life exposures impacting OPV immunization by measuring OPV response for serotypes 1 and 3. Methods: Polio neutralizing antibody assays were conducted at 7 and 15 months of age for serotypes 1 and 3. Analyses were conducted on children receiving >= 3 OPV doses (n = 1449). History of vaccination, feeding patterns, physical growth, home environment, diarrhea, enteropathogen detection, and gut inflammation were examined as risk factors for non-response [Log(2)(titer)< 3] and Log(2)(titer) by serotype using multivariate regression. Findings: Serotype 1 seroconversion was significantly higher than serotype 3 (96.6% vs. 89.6%, 15 months). Model results indicate serotypes 1 and 3 failure was minimized following four and six OPV doses, respectively;however, enteropathogen detection and poor socioeconomic conditions attenuated response in both serotypes. At three months of age, bacterial detection in stool reduced serotype 1 and 3 Log(2) titers by 0.34 (95% CI 0.14-0.54) and 0.53 (95% CI 0.29-0.77), respectively, and increased odds of serotype 3 failure by 3.0 (95% CI 1.6-5.8). Our socioeconomic index, consisting of Water, Assets, Maternal education, and Income (WAMI), was associated with a 0.79 (95% CI 0.15-1.43) and 1.23 (95% CI 034-2.12) higher serotype 1 and 3 Log(2) titer, respectively, and a 0.04 (95% CI 0.002-0.40) lower odds of serotype 3 failure. Introduction of solids, transferrin receptor, and underweight were differentially associated with serotype response. Other factors, including diarrheal frequency and breastfeeding practices, were not associated with OPV response. Interpretation: Under real-world conditions, improved vaccination coverage and socio-

关键词： sIPV   Sabin strain   Direct deep-sequencing   Genetic stability  

摘要： Inactivated poliomyelitis vaccine made from Sabin strains (sIPV) has been encouraged to introduce in the "Global Polio Eradication & Endgame Strategic Plan" and increasingly used worldwide. Attenuated Sabin strains used in manufacture of oral poliovirus vaccine (OPV) and sIPV may regain full or partial neurovirulence during growth in vaccine recipients and the vaccine manufacturing processes. Ensuring the molecular consistency of sIPV batches and that no mutation accumulates beyond the level present in past batches are important for quality control of vaccine manufacture process. Direct deep-sequencing allows the construction of a library of virus RNA and the detection of genetic mutations throughout the viral genome. In the present study, direct deep-sequencing was conducted to detect molecular mutations in virus passages, multiple sIPV monovalent lots, and virus monovalent lots from different polio type Ill strains. The results indicated that direct deep-sequencing can be used to identify and quantify small amounts of mutant viruses in vaccine preparations, trace the source of a specific virus seed, and monitor the batch-to-batch consistency of vaccines, suggesting that this technique could be suitable for the quality control and consistency monitoring of sIPV production. (C) 2018 Elsevier Ltd. All rights reserved.

关键词： inactivated polio vaccine (IPV)   pH   phenol red   stabilization   zeta potential  

摘要： To analyze the effects of phenol red at various pH values on the Sabin type 2 inactivated polio vaccine (sIPV2), several biophysical techniques were used to evaluate the particle size and capsid protein for conformation. sIPV2's size was assessed via transmission electron microscopy and dynamic light scattering. The effects of various pH values (from 4.0 to 7.0) on the biophysical characters of sIPV2 particles in solution were determined by dynamic light scattering and zeta potential. The results clearly indicated that aggregation and instability occurred in the solution of sIPV2 particles at a pH of 6.0. Under similar conditions, by dynamic light scattering and zeta potential, the virus particles in solution showed more dispersion and were stable with the addition of 0.05 mM phenol red. According to circular dichroism and intrinsic tryptophan fluorescence data, it was observed that the secondary and tertiary structures of the sIPV2 particles were more stable with the protection of phenol red. At a pH below 6.0, the sIPV2 solution with phenol red had more D-antigen content, which was confirmed by enzyme-linked immunosorbent assay and rat experiments. These results strongly suggested that phenol red improved the pH stability of the sIPV2. The study indicated the potential of phenol red in preserving vaccine potency of the sIPV2 at various pH values.

关键词： adjuvant   geometric mean titer   long duration   polio vaccine   seroconversion  

摘要： Background At the same dosage, the new generation of Sabin-inactivated poliovirus vaccine (sIPV) is less immunogenic than the traditional oral polio vaccine (OPV) dosage in China. The useful adjuvant might be a necessary strategy to strengthen the immune protective effects. Methods Results In this study, we produced an adjuvant compound (named KML05) that could promote immunogenicity and fractional doses of sIPV with a long duration of protection in a rat model. The compound adjuvant had both advantages and a function of MF59 and carbopol971P. The effect seroconversion of experimental animals immunized with KML05 could be extended to one-eighth of the dose. According to the result of the geometric mean titers (GMTs), KML05 adjuvant could save eight times the amount of sIPV D-antigen usage, but aluminum hydroxide adjuvant could save twice at the same titers. Additionally, it was found that there was a significant difference in the GMT titer of poliovirus type 2 between animals immunized by KML05 and alum adjuvant (P < 0.05). At 12th-month postvaccination, the neutralization titers stimulated by IPV-KML05 were maintained over a longer time period in immunized animals. Conclusion Our research team developed KML05 adjuvant, which combined carbopol971P with MF59, increased antibody responses to sIPV for a longer duration of protection in a rat model.

关键词： 脊髓灰质炎灭活疫苗   脊髓灰质炎减毒活疫苗   序贯免疫   粪便排毒  

摘要： 目的 本研究旨在讨论脊髓灰质炎疫苗不同序贯免疫的接种效果和排毒情况,为制定合理的脊髓灰质炎疫苗免疫程序提供依据;并比较了不同的脊髓灰质炎检测方法,为选择合理的脊髓灰质炎病毒检测方法提供参考。方法 选取广西壮族自治区1200名2～3月龄健康的未接种过脊灰疫苗的婴幼儿,随机分为IPV和OPV序贯免疫组,共12组,每组100人,在第0、28、56天接种相应疫苗,在免前和基础免疫后28天检测血清中脊灰各型抗体阳转率和抗体滴度,并随机抽取各组入组时前10%的受试对象在第二剂接种前和第二、三接种后第7、14、28天进行粪便采集,总共7次,所有的粪便样本通过L20B和RD两种细胞系进行分离培养,通过中和试验对细胞培养物中脊灰病毒进行血清型别鉴定。比较各序贯免疫程序组不同时期各型病毒的排毒率情况。第二部分从上述免疫程序组每组抽取6个粪便样本,通过实时荧光定量PCR法检测粪便上清中脊灰病毒的排毒情况,并与细胞培养法进行比较,分别用ELISA、RT-PCR对细胞培养物中的脊灰病毒进行型内鉴定,比较中和试验、ELISA、RT-PCR三种方法分型结果的一致性。结果 排除脱落与其他不符合实验方案的受试者,总共2062份配对血清和806份粪便样本进入统计学分析。12个序贯免疫组各组免前脊灰各型抗体阳性率和GMT均无统计学差异。相同免疫程序不同剂型免后脊灰各型抗体阳转率和GMT均无显著差异。相同剂型不同免疫程序免后Ⅰ、Ⅲ型抗体阳转率组间比较均无显著差异,2IPV+bOPV组免后脊灰Ⅰ、Ⅲ型抗体GMT均高于其他组;接种2剂IPV后Ⅱ型抗体阳转率和GMT显著升高。cIPV/OPV序贯免疫组与sIPV/OPV序贯免疫组相同免疫程序免后各型脊灰抗体阳转率均无统计学差异;sIPV/OPV序贯免疫组免后Ⅰ型抗体GMT均高于相同免疫程序的cIPV/OPV序贯免疫组,Ⅱ型抗体低于cIPV/OPV序贯免疫组,接种2剂sIPV后与cIPV/OPV序贯免疫组无显著差异;IPV/OPV序贯免疫组与sIPV/OPV序贯免疫组免后Ⅲ型抗体GMT无显著差异。各免疫程序组在接种首剂OPV后7天内排毒率达到最高峰,随后排毒率逐渐降低。首剂OPV接种后3周内均出现任意一型病毒的排毒,且Ⅲ型脊灰病毒排毒率最高。各免疫程序组Ⅰ、Ⅱ型脊灰病毒排毒率无显著差异;sIPV+2bOPV组Ⅲ型病毒总排毒率显著高于 2sIPV+bOPV 组与 2sIPV+tOPV 组,cIPV+2bOPV 液体组显著高于 2cIPV+tOPV液体组。细胞培养法检测出的阳性样本用实时荧光定量PCR法均能检测出来,且实时荧光定量PCR法检测的阳性结果更多;中和试验、ELISA、RT-PCR三种方法对细胞培养物中脊灰病毒的分型结果无显著差异。结论 脊灰疫苗基础免疫效果受到不同序贯免疫程序的影响,2剂IPV免疫效果优于1剂IPV,尤其是Ⅱ型。不同的脊髓灰质炎序贯免疫排毒情况有差异,IPV剂次增加虽然不能显著降低排毒率,但能缩短各型病毒的排毒时间。实时荧光定量PCR法对原始粪便标本中脊灰病毒的检出率比细胞培养法更高,但无法判断病毒是否具有感染性,因此样本量较大时可以用来初步筛选出阳性样本,然后再用细胞培养法进行检测。中和试验、ELISA、RT-PCR三种方法对脊灰病毒的分型结果一致性很高,可以使用后面的两种方法替代经典的中和试验法来对细胞培养物中的脊灰病毒进行型内鉴定。

关键词： virus   epidemic   energy   exergy   host cell rupture  

摘要： Poliovirus is an RNA virus which proliferate itself in the intestines. Thermodynamic assessment of the proliferation process has been assessed after calculating the energy and exergy of the RNA with the group contribution method. Mass, energy and exergy balances are performed to calculate the energy and exergy exploited from the host cell as 4.65 x 10(-19) and 3.35 x 10(-17) kJ, respectively. In a typical epidemic in 1988, 350,000 cases were reported, implying that the total of 1.627 x 10(-9) kJ of energy 1.174 x 10(-7) kJ of exergy was exploited from them during the epidemic. Although the energy and exergy efficiency of virus generation in a host cell were very small, e.g., 1.376 x 10(-6) and 9.78 x 10(-5), respectively;energy and exergy employed in this process was very small implying that extremely small energy and exergy requirement by poliovirus to proliferate itself is the key to an outbreak of an epidemic.

关键词： 急性弛缓性麻痹   疫苗免疫程序转换   流行特征   病原学监测  

摘要： 目的:分析比较河北省脊髓灰质炎（poliomyelitis,脊灰）疫苗免疫程序转换前后急性弛缓性麻痹（acute flaccid paralysis,AFP）病例流行特征,评价脊灰疫苗免疫程序转换的效果,为继续调整脊灰疫苗免疫策略、消灭脊灰提供科学依据。方法:1.采用描述性流行病学方法比较分析河北省脊灰疫苗免疫程序转换前后两年（2014年5月2016年4月与2016年5月2018年4月）AFP病例的流行病学和病原学特征。2.采用人横纹肌肉瘤细胞（RD细胞）、转人脊灰病毒受体基因的小鼠肺细胞（L20B细胞）分离脊灰病毒,细胞病变效应阳性分离物采用实时荧光定量RT-PCR方法进行型内鉴定;采用细胞中和抗体试验检测血清脊灰中和抗体水平。3.采用SPSS21.0软件进行统计检验:率、构成比的比较采用卡方检验和Fisher's确切概率法,等级资料的比较采用秩和检验,脊灰中和抗体水平比较采用方差分析,检验水准α=0.05;多变量影响因素分析采用Logistic回归。结果:1.脊灰疫苗免疫程序转换前后河北省AFP病例分别报告652例、633例,15岁以下儿童报告发生率分别为2.49/10万、2.26/10万（χ2=2.903,P=0.088）。2.脊灰疫苗免疫程序转换前后0～4岁AFP病例占比分别为63.50%、54.98%,比较年龄构成（Z=-3.438,P=0.001）;男女性别比分别为1.72:1、1.30:1（χ2=5.886,P=0.015）;各月份、各地市病例均散在分布。AFP病例60d残留麻痹率分别为14.72%、16.27%（χ2=0.588,P=0.443）。3.脊灰疫苗免疫程序转换前河北省报告疫苗相关麻痹型脊灰（Vaccine-associated Paralytic Poliomyelitis,VAPP）病例4例、脊灰疫苗衍生病毒（Vaccine-derived Polio virus,VDPV）病例1例,转换后无VAPP病例、VDPV病例的报告。4.脊灰疫苗免疫程序转换前后AFP病例脊灰病毒阳性分离率分别为2.91%、1.26%（χ2=4.252,P=0.039）,血清型分别是Ⅰ型（7株）、Ⅱ型（11株）、Ⅲ型（4株）和Ⅰ型（5株）、Ⅲ型（5株）(P=0.010)。非脊灰肠道病毒（Non-polio entervirus,NPEV）分离率阳性分别为14.88%、12.95%（χ2=0.002,P=0.960）。5.2012～2016年河北省0～2岁儿童Ⅰ型、Ⅱ型、Ⅲ型脊灰中和抗体几何平均滴度（Geometric Mean Titer,GMT）分别为1:216.93、1:217.18和1:168.04;2017～2018年Ⅰ型、Ⅲ型GMT分别为1:237.15、1:114.71;脊灰疫苗免疫程序转换前后Ⅰ型（F=0.091,P=0.764）、Ⅲ型（F=0.687,P=0.408）GMT比较差异无统计学意义。结论:1.河北省脊灰疫苗免疫程序转换前后脊灰中和抗体GMT水平未发生改变,AFP病例的季节、地区分布、NEPV阳性分离率、AFP病例60天残留麻痹率等流行特征未发生改变。2.河北省脊灰疫苗免疫程序转换后无VAPP、VDPV病例的报告,AFP病例PV阳性分离率下降。

关键词： 顾方舟   活疫苗   脊髓灰质炎病毒  

摘要： 顾方舟从31岁开始,就努力在中国消灭导致小儿麻痹症的脊髓灰质炎病毒,为此花了40余年时间。他在中国研制出首批脊灰活疫苗,并把疫苗包裹进糖丸中,以便送到农村和偏远地区。2000年,世界卫生组织宣布中国消灭脊髓灰质炎病毒时,顾方舟曾作为代表在证实报告上签字,但他从来没因此放弃警惕。他研制的糖丸已经被证明可以明