关键词： oral poliovirus vaccine   immunogenicity   serologic response   buffer  

摘要： Background. Polio eradication efforts have been hampered by low responses to trivalent oral poliovirus vaccine (tOPV) in some developing countries. Since stomach acidity may neutralize vaccine viruses, we assessed whether administration of a buffer solution could improve the immunogenicity of tOPV. *** integral Healthy infants 4-6 weeks old in Sylhet, Bangladesh, were randomized to receive tOPV with or without a sodium bicarbonate and sodium citrate buffer at age 6, 10, and 14 weeks. Levels of serum neutralizing antibodies for poliovirus types 1, 2, and 3 were measured before and after vaccination, at 6 and 18 weeks of age, respectively. *** integral Serologic response rates following 3 doses of tOPV for buffer recipients and control infants were 95% and 88% (P = .065), respectively, for type 1 poliovirus;95% and 97% (P = .543), respectively, for type 2 poliovirus;and 90% and 89% (P = .79), respectively, for type 3 poliovirus. *** integral Administration of a buffer solution prior to vaccination was not associated with statistically significant increases in the immune response to tOPV;however, a marginal 7% increase (P = .065) in serologic response to poliovirus type 1 was observed. Clinical Trials *** integral NCT01579825.

关键词： 脊髓灰质炎病毒   D抗原   C抗原   单克隆抗体  

摘要： 目的制备脊髓灰质炎病毒2型(PV2)和3型(PV3)D抗原的单克隆抗体(mAb),并对抗体的特性进行初步鉴定。方法以PV2及PV3的D抗原为免疫原,常规方法制备小鼠源性mAb,用间接ELISA检测小鼠腹水效价、型别特异性及与C抗原的交叉反应。结果获得4株PV2特异性并与PV2的C抗原不交叉的mAb,2株PV3特异性并与PV3的C抗原不交叉的mAb。结论成功制备了PV2及PV3特异性并与C抗原不交叉的D抗原mAb。

关键词： inactivated poliovirus vaccine   affordability   intradermal administration   production optimization   adjuvant   schedule reduction   further attenuated poliovirus strains  

摘要： After polio eradication is achieved, the use of live-attenuated oral poliovirus vaccine (OPV) must be discontinued because of the inherent risk of the Sabin strains to revert to neurovirulence and reacquire greater transmissibility that could potentially result in the reestablishment of polio transmission. In 2008, the World Health Assembly mandated that the World Health Organization establish a strategy for developing more-affordable inactivated poliovirus vaccine (IPV) options for low-income countries. In 2012, the Strategic Advisory Group of Experts (SAGE) on Immunization recommended universal IPV introduction as a risk-mitigation strategy before the phased cessation of OPV (starting with Sabin type 2) and emphasized the need for affordable IPV options. In 2013, SAGE reiterated the importance of attaining the long-term target price of IPV at approximately $0.5 per immunizing dose and encouraged accelerated efforts to develop lower-cost IPV options. This article outlines the 4-pronged approach that is being pursued to develop affordable options and provides an update on the current status and plans to make IPV affordable for developing-country use.

关键词： wild poliovirus   silent poliovirus transmission   environmental surveillance   emergency health policy response   epidemiology   vaccine   molecular analysis  

摘要： Wild poliovirus type 1 (WPV1) introduction into southern Israel in early 2013 was detected by routine environmental surveillance. The virus was identified genetically as related to the South Asian (SOAS) R3A lineage endemic to Pakistan in 2012. Intensified, high-throughput environmental surveillance using advanced molecular methods played a critical role in documenting and locating sustained transmission throughout 2013 and early 2014 in the absence of any acute flaccid paralysis. It guided the public health responses, including stool-based surveillance and serosurveys, to determine the point prevalence in silent excretors and measured the effect of vaccination campaigns with inactivated polio vaccine and bivalent oral polio vaccine on stopping transmission.

关键词： Free energy   Peptides and proteins   Genetics   Photovoltaics   Noncovalent interactions  

摘要： RNA-dependent RNA polymerases (RdRps) are enzymes catalyzing RNA replication from a RNA template. Active-site closure in RdRps, normally induced by correct nucleotide triphosphate (NTP) binding, is a prerequisite for the cycle of nucleotide incorporation. So, a complete understanding of polymerase function (in particular polymerase fidelity) of a RdRp requires more complete knowledge of active-site closure in the RdRp. In this work, based on solved crystal structures, we have built different models for the RNA-dependent RNA polymerase from poliovirus (termed PV 3D(pol)). Through MD simulations and free energy calculations of these PV 3Dpol models, we have revealed the dynamic correlation between motif A and motif D and between motif A and incoming NTP, have deepened our understanding of polymerase fidelity from dynamic aspects, and have provided an explanation to the puzzle that arises from different observations based on kinetic studies and structural data.

关键词： RNA secondary structure   post transcriptional RNA processing   3 ' NCR   protein expression  

摘要： Enrichment of production yield of therapeutic proteins in mammalian cell cultures by modulation of the mRNA stability of the target protein to increase its in vivo half-life is a new strategy in biotechnological applications. The present article describes one of the most novel approaches to modulate mRNA stability by application of 3'-noncoding region (3'NCR) from RNA viral genome in the expression constructs. Our data indicated that although utilizing the 3'NCR sequence form poliovirus (PV-3'NCR) downstream of the target gene might generally stabilize the secondary structure of RNA, it influenced the mRNA stability (and thereby the amount of protein production) in a cell type and time-dependent manner, thus indicating a central role of mRNA-stabilizing binding sites/cellular factors in this process. Our data might be of interest to the biotechnology community to improve recombinant protein production in mammalian cell cultures and RNA-based therapy/vaccination approaches. (c) 2014 International Union of Biochemistry and Molecular Biology, Inc.

关键词： Electrolytes   Proteins   Molecular dynamics   Surface charge   High pressure  

摘要： Small viruses that belong, for example, to the Picornaviridae, such as poliovirus and foot-and-mouth disease virus, consist simply of capsid proteins and a single-stranded RNA (ssRNA) genome. The capsids are quite stable in solution to protect the genome from the environment. Here, based on longtime and large-scale 6.5 x 10(6) all-atom molecular dynamics calculations for the Mahoney strain of poliovirus, we show microscopic properties of the viral capsids at a molecular level. First, we found equilibrium rapid exchange of water molecules across the capsid. The exchange rate is so high that all water molecules inside the capsid (about 200 000) can leave the capsid and be replaced by water molecules from the outside in about 25 mu s. This explains the capsid's tolerance to high pressures and deactivation by exsiccation. In contrast, the capsid did not exchange ions, at least within the present simulation time of 200 ns. This implies that the capsid can function, in principle, as a semipermeable membrane. We also found that, similar to the xylem of trees, the pressure of the solution inside the capsid without the genome was negative. This is caused by coulombic interaction of the solution inside the capsid with the capsid excess charges. The negative pressure may be compensated by positive osmotic pressure by the solution-soluble ssRNA and the counter ions introduced into it. (C) 2014 AIP Publishing LLC.

关键词： Female   Humans   Male   Poliomyelitis/prevention & control   Poliomyelitis/prevention & control   Poliovirus Vaccine, Inactivated/administration & dosage  

摘要： Successful globally coordinated cessation of OPV will lead to achievement of the ultimate goal from 1988 to end all cases of poliomyelitis, at which time IPV will represent the only polio vaccine option.3 Unfortunately, a recent independent review by the Independent Monitoring Board of the Global Polio Eradication Initiative suggested that many challenges remain.5 Current epidemiological experience extends the trend observed since 2000, with 50 different countries that successfully stopped all wild poliovirus transmission within their borders at some point in time reporting one or more paralytic polio cases between 2000 and 2012 due to imported wild polioviruses.6 Specifically, in 2014, seven countries reported cases of wild poliovirus 1 associated with importations (as of May), including two countries that stopped indigenous wild poliovirus transmission before the year 2000 (ie, Syria and Equatorial Guinea).5 Israel, which maintained high routine immunisation coverage with an IPV only schedule from 2005 to 2013, also reported the detection of circulating imported wild poliovirus7 that extended through the end of March, fortunately without any cases.5 Recently, Brazil reported detection of imported wild poliovirus 1 in a sewage sample, which was genetically similar to the circulating virus in Equatorial Guinea.8 Achievement of the goal of wild poliovirus eradication and successful transition to a world free of poliomyelitis requires ongoing national, regional, and global commitments to maintain high population immunity to poliovirus transmission.9 In view of the inability to easily measure population immunity or extrapolate from individual immunity to population immunity, policy makers can look to models for some decision support.9,10 An expert review of the literature on polio immunity and transmission showed the need for models of poliovirus transmission to include sufficient complexity to deal with the reality that IPV offers little or no enteric mucosal immunity

摘要： Background Intestinal immunity induced by oral poliovirus vaccine (OPV) is imperfect and wanes with time, permitting transmission of infection by immunised children. Inactivated poliovirus vaccine (IPV) does not induce an intestinal mucosal immune response, but could boost protection in children who are mucosally primed through previous exposure to OPV. We aimed to assess the effect of IPV on intestinal immunity in children previously vaccinated with OPV. Methods We did an open-label, randomised controlled trial in children aged 1-4 years from Chinnallapuram, Vellore, India, who were healthy, had not received IPV before, and had had their last dose of OPV at least 6 months before enrolment. Children were randomly assigned (1: 1) to receive 0.5 mL IPV intramuscularly (containing 40, 8, and 32 D antigen units for serotypes 1, 2, and 3) or no vaccine. The randomisation sequence was computer generated with a blocked randomisation procedure with block sizes of ten by an independent statistician. The laboratory staff did blinded assessments. The primary outcome was the proportion of children shedding poliovirus 7 days after a challenge dose of serotype 1 and 3 bivalent OPV (bOPV). A second dose of bOPV was given to children in the no vaccine group to assess intestinal immunity resulting from the first dose. A per-protocol analysis was planned for all children who provided a stool sample at 7 days after bOPV challenge. This trial is registered with Clinical Trials Registry of India, number CTRI/2012/09/003005. Findings Between Aug 19, 2013, and Sept 13, 2013, 450 children were enrolled and randomly assigned into study groups. 225 children received IPV and 225 no vaccine. 222 children in the no vaccine group and 224 children in the IPV group had stool samples available for primary analysis 7 days after bOPV challenge. In the IPV group, 27 (12%) children shed serotype 1 poliovirus and 17 (8%) shed serotype 3 poliovirus compared with 43 (19%) and 57 (26%) in the no vaccine gr

关键词： Acceptability   Childhood immunization   Inactivated polio vaccine   Nigeria  

摘要： Background: The introduction of inactivated polio vaccines (IPV) is imminent. In view of the Polio Eradication and Endgame Strategic Plan 2013-2018, parental acceptance of IPV will be important for achieving universal coverage. In view of the imminent introduction of IPV, it is only reasonable to assess the awareness and acceptance of IPV, so that necessary socio-anthropological measures would be put in place. This study is aimed at determining the level of awareness and acceptance of IPV by parents. Methods: A cross-sectional study involving 408 parents that brought their children for immunization. Structured-questionnaire was to collect data on the parent's demographic characteristics, awareness and acceptance of IPV. The independent factors that may affect parental acceptability of IPV were evaluated using linear regression analysis. Results: About 53% of the parents had no knowledge of vaccine content and 84.1% had not heard of IPV, and 40.2% were willing to accept IPV. However, with post-intervention (IPV) health education, the level of acceptance of IPV increased to 95.6% and the difference was statistically significant (p = 0.0001). 35.3% expressed fear for IPV, and 61.8% cited fear for pain (61.8%). In the rating scale of 1 to 5, doctors (4.7), Nurses (4.0) and staff of the Ministry of Health (4.0) were rated high as reliable media to inform them about a new vaccine. The logistic regression revealed only educational level of mothers (p-value = 0.048) was the only significant factor associated with acceptability of IPV. Conclusion: The parents' knowledge on vaccine was poor, as well as IPV acceptability (pre health education). But the acceptability was improved with provision of extra information. Although most still preferred OPV, and with improvement in pain management, acceptability of IPV can be improved further. Clear policies and strategies should be immediately developed and implementation of pre-introduction awareness/sensitization on IPV should be co