关键词： 二价脊髓灰质炎减毒活疫苗   疑似预防接种异常反应   安全性  

摘要： 目的评价河北省二价脊髓灰质炎减毒活疫苗（bOPV）预防接种的安全性。方法通过全国疑似预防接种异常反应（AEFI）监测信息管理系统收集河北省2017年bOPV的AEFI报告数据,进行描述性分析。结果河北省2017年共报告bOPV的AEFI 590例,报告发生率为22.02/10万剂,其中一般反应、异常反应分别占95.25%（562例,20.98/10万剂）、3.39%（20例,0.75/10万剂）;≤1岁占70.34%;发生在接种疫苗后≤1d内占87.63%。结论河北省bOPV预防接种安全性良好。

关键词： WHO  

摘要： Background The prognosis of patients with recurrent World Health Organization(WHO)grade IV malignant glioma is dismal,and there is currently no effective *** conducted a dose-finding and toxicity study in this population of patients,evaluating convection-enhanced,intratumoral delivery of the recombinant nonpathogenic polio-rhinovirus chimera(PVSRIPO).PVSRIPO recognizes the poliovirus receptor CD155,which is widely expressed in neoplastic cells of solid tumors and in major components of the tumor *** We enrolled consecutive adult patients who had recurrent supratentorial WHO grade IV malignant glioma,confirmed on histopathological testing,with measurable disease(contrast-enhancing tumor of≥1 cm and≤5.5 cm in the greatest dimension).The study evaluated seven doses,ranging between 107 and 1010 50%tissue-culture infectious doses(TCID50),first in a dose-escalation phase and then in a dose-expansion *** From May 2012 through May 2017,a total of 61 patients were enrolled and received a dose of *** level-1(5.0×107TCID50)was identified as the phase 2 *** dose-limiting toxic effect was observed;a patient in whom dose level 5(1010TCID50)was administered had a grade 4 intracranial hemorrhage immediately after the catheter was *** mitigate locoregional inflammation of the infused tumor with prolonged glucocorticoid use,dose level 5 was deescalated to reach the phase 2 *** the dose-expansion phase,19%of the patients had a PVSRIPO-related adverse event of grade 3 or *** survival among the patients who received PVSRIPO reached a plateau of 21%(95%confidence interval,11 to 33)at 24 months that was sustained at 36 *** Intratumoral infusion of PVSRIPO in patients with recurrent WHO grade IV malignant glioma confirmed the absence of neurovirulent *** survival rate among patients who receivedPVSRIPO immunotherapy was higher at 24 and 36 months than the rate among historical controls.

关键词： Polio vaccine   D-antigen recovery   Spray drying   Atomization stress and dry powder  

摘要： The objective of this study was to develop a stable spray dried formulation, containing the three serotypes of Sabin inactivated polio vaccine (sIPV), aiming for minimal loss of native conformation (D-antigen) during drying and subsequent storage. The influence of atomization and drying stress during spray drying on trivalent sIPV was investigated. This was followed by excipient screening, in which monovalent sIPV was formulated and spray dried. Excipient combinations and concentrations were tailored to maximize both the antigen recovery of respective sIPV serotypes after spray drying and storage (T = 40 degrees C and t = 7 days). Furthermore, a fractional factorial design was developed around the most promising formulations to elucidate the contribution of each excipient in stabilizing D-antigen during drying. Serotype 1 and 2 could be dried with 98% and 97% recovery, respectively. When subsequently stored at 40 degrees C for 7 days, the D-antigenicity of serotype 1 was fully retained. For serotype 2 the D-antigenicity dropped to 71%. Serotype 3 was more challenging to stabilize and a recovery of 56% was attained after drying, followed by a further loss of 37% after storage at 40 degrees C for 7 days. Further studies using a design of experiments approach demonstrated that trehalose/monosodium glutamate and maltodextrin/arginine combinations were crucial for stabilizing serotype 1 and 2, respectively. For sIPV serotype 3, the best formulation contained Medium199, glutathione and maltodextrin. For the trivalent vaccine it is therefore probably necessary to spray dry the different serotypes separately and mix the dry powders afterwards to obtain the trivalent vaccine.

关键词： Dynamic modeling   polio eradication   risk management  

摘要： Abstract: Due to security, access, and programmatic challenges in areas of Pakistan and Afghanistan, both countries continue to sustain indigenous wild poliovirus (WPV) transmission and threaten the success of global polio eradication and oral poliovirus vaccine (OPV) cessation. We fitted an existing differential‐equation‐based poliovirus transmission and OPV evolution model to Pakistan and Afghanistan using four subpopulations to characterize the well‐vaccinated and undervaccinated subpopulations in each country. We explored retrospective and prospective scenarios for using inactivated poliovirus vaccine (IPV) in routine immunization or supplemental immunization activities (SIAs). The undervaccinated subpopulations sustain the circulation of serotype 1 WPV and serotype 2 circulating vaccine‐derived poliovirus. We find a moderate impact of past IPV use on polio incidence and population immunity to transmission mainly due to (1) the boosting effect of IPV for individuals with preexisting immunity from a live poliovirus infection and (2) the effect of IPV‐only on oropharyngeal transmission for individuals without preexisting immunity from a live poliovirus infection. Future IPV use may similarly yield moderate benefits, particularly if access to undervaccinated subpopulations dramatically improves. However, OPV provides a much greater impact on transmission and the incremental benefit of IPV in addition to OPV remains limited. This study suggests that despite the moderate effect of using IPV in SIAs, using OPV in SIAs remains the most effective means to stop transmission, while limited IPV resources should prioritize IPV use in routine immunization. [ABSTRACT FROM AUTHOR]

关键词： PHOSPHOLIPID synthesis   POLIOVIRUS   VIRAL replication   PREVENTION   PICORNAVIRUS infections   ORGANELLES  

摘要： Rapid development of complex membranous replication structures is a hallmark of picornavirus infections. However, neither the mechanisms underlying such dramatic reorganization of the cellular membrane architecture, nor the specific role of these membranes in the viral life cycle are sufficiently understood. Here we demonstrate that the cellular enzyme CCT alpha, responsible for the rate-limiting step in phosphatidylcholine synthesis, translocates from the nuclei to the cytoplasm upon infection and associates with the replication membranes, resulting in the rerouting of lipid synthesis from predominantly neutral lipids to phospholipids. The bulk supply of long chain fatty acids necessary to support the activated phospholipid synthesis in infected cells is provided by the hydrolysis of neutral lipids stored in lipid droplets. Such activation of phospholipid synthesis drives the massive membrane remodeling in infected cells. We also show that complex membranous scaffold of replication organelles is not essential for viral RNA replication but is required for protection of virus propagation from the cellular anti-viral response, especially during multi-cycle replication conditions. Inhibition of infection-specific phospholipid synthesis provides a new paradigm for controlling infection not by suppressing viral replication but by making it more visible to the immune system.

关键词： lyophilization   inactivated polio vaccine   thermal stability   potency   urea  

摘要： Stable formulations of inactivated polio vaccine (IPV) could reduce cold-chain requirements and increase distribution of the vaccine to developing countries. Recently, significant improvement in thermal stability of IPV vaccines has been achieved by including urea in lyophilized formulations. In the present study, we investigated the effects of urea on recovery of potency of IPV after lyophilization and storage at 37 degrees C and the correlation of potency recovery with key biophysical properties of IPV. By dynamic light scattering and transmission light microscopy, we found that loss of potency appeared to be due to agglomeration of virus particles during lyophilization and that moderate concentrations (e.g., 0.4 M) of urea reduced agglomeration and improved potency recovery. In addition, the relative thermal stability of the viron proteins was assessed after rehydration with temperature-dependent intrinsic fluorescence. Lyophilization of formulations without urea and postdrying storage resulted in reduced apparent melting temperatures in rehydrated samples. In formulations with urea, the rehydrated samples had thermal transitions and melting temperatures that were similar to those observed in aqueous control samples. Overall, the results indicated that in IPV formulations, urea improved potency recovery by inhibiting viron particle agglomeration and reducing denaturation of viron proteins. (C) 2018 American Pharmacists Association (R). Published by Elsevier Inc. All rights reserved.

关键词： Poliomyelitis   Immunity   Solid organ transplant  

摘要： Objectives: To assess the prevalence of protective antibody titers to polioviruses in adults candidates for solid organ transplant (SOT), and to assess the immunogenic response to inactivated polio vaccine in this population. Methods: The study included SOT candidates referred to Immunization Reference Centre of Evandro Chagas National Institute of Infectious Diseases from March 2013 to January 2016. It was conducted in 2 phases. The first one, a cross-sectional seroprevalence study, followed by an uncontrolled analysis of vaccine response among patients without protective antibody titers at baseline. Antibody titers to poliomyelitis were determined by microneutralization assay. Results: Among 206 SOT candidates included, 156 (76%) had protective antibody titers to all poliovirus serotypes (95% CI: 70-81%). Proven history of oral vaccination in childhood was not associated with higher seroprevalence of protective antibody. In 97% of individuals without protective antibody titers at baseline, there was adequate vaccine response with one dose of inactivated polio vaccine. Conclusions: A relevant proportion of adult candidates for SOT does not have protective titers of antibodies to one or more poliovirus serotype. One dose of inactivated vaccine elicited protective antibody titers in 97% of these subjects and should be routinely prescribed prior to SOT. (C) 2018 Elsevier Ltd. All rights reserved.

关键词： Polio   Outbreak   Vaccination   Vaccine   Somalia  

摘要： Background: Using a survey conducted during the 2013-2014 polio outbreak in Somalia, this study examines attitudinal and knowledge-based threats to oral polio vaccine acceptance and commitment. Findings address a key gap, as most prior research focuses on endemic settings. Methods: Between November 19 and December 21, 2013, we conducted interviews among 2003 care givers of children under 5 years in select districts at high risk for polio transmission. Within each district, sample was drawn via a multi-stage cluster design with random route household selection. We calculated the percentage of caregivers who could not confirm recent vaccination and those uncommitted to future vaccination. We compared these percentages among caregivers with varying knowledge and attitudes, focusing on variables identified as threats in endemic settings, using controlled and uncontrolled comparisons. We also examined absolute levels of threat variables. Results: Only 10% of caregivers could not confirm recent vaccination, but 32% were uncommitted to future vaccination. Being unvaccinated or uncommitted were related to multiple threat variables. For example, compared with relevant counterparts, caregivers were more likely to be unconfirmed and uncommitted if they did not trust vaccinators "a great deal" (unconfirmed: 9% vs. 2%;uncommitted: 49% vs. 28%), which is also true in endemic settings. Unlike endemic settings, symptom knowledge was related to commitment while rumor awareness was low and unrelated to past acceptance or commitment. Levels of trust and perceptions of OPV effectiveness were high, though perceptions of community support and awareness of logistics were lower. Conclusions: As in endemic settings, outbreak responses will benefit from communications strategies focused on enhancing trust in vaccinators, institutions and the vaccine, alongside making community support visible. Disease facts may help motivate acceptance, and enhanced logistics information may help facilitate

摘要： The article reports on the usage of oral poliovirus vaccine (OPV) by the countries after declaration of eradication of wild poliovirus type 2 in 2015. Topics discussed include prevention of trivalent OPV (tOPV) usage; information on the acute flaccid paralysis (AFP) surveillance, an indicator of the sensitivity of surveillance to detect polio; and the detection of a genetically related type 2 vaccine-derived polioviruses (VDPV2) isolate from a sewage sample collected from Banadir, Somalia.