关键词： Infectious disease   Diagnostics   Epidemiology   PCR   Hybridization array   Poliovirus   Influenza  

摘要： We evaluate sequence data from the PathChip high-density hybridization array for epidemiological interpretation of detected pathogens. For influenza A, we derive similar relative outbreak clustering in phylogenetic trees from PathChip-derived compared to classical Sanger-derived sequences. For a positive polio detection, recent infection could be excluded based on vaccine strain similarity. (C) 2016 The Authors. Published by Elsevier Inc. This is an open access article under the CC BY-NC-ND license.

关键词： Viral vaccines   Viral replication   Poliovirus   Microbial mutation   Antigens   Internal ribosome entry site   Attenuated vaccines   Mouse models  

摘要： The poliovirus vaccine field is moving towards novel vaccination strategies. Withdrawal of the Oral Poliovirus Vaccine and implementation of the conventional Inactivated Poliovirus Vaccine (cIPV) is imminent. Moreover, replacement of the virulent poliovirus strains currently used for cIPV with attenuated strains is preferred. We generated Cold-Adapted Viral Attenuation (CAVA) poliovirus strains by serial passage at low temperature and subsequent genetic engineering, which contain the capsid sequences of cIPV strains combined with a set of mutations identified during cold-adaptation. These viruses displayed a highly temperature sensitive phenotype with no signs of productive infection at 37 degrees C as visualized by electron microscopy. Furthermore, decreases in infectious titers, viral RNA, and protein levels were measured during infection at 37 degrees C, suggesting a block in the viral replication cycle at RNA replication, protein translation, or earlier. However, at 30 degrees C, they could be propagated to high titers (9.4-9.9 Log(10)TCID(50)/ml) on the PER. C6 cell culture platform. We identified 14 mutations in the IRES and non-structural regions, which in combination induced the temperature sensitive phenotype, also when transferred to the genomes of other wild-type and attenuated polioviruses. The temperature sensitivity translated to complete absence of neurovirulence in CD155 transgenic mice. Attenuation was also confirmed after extended in vitro passage at small scale using conditions (MOI, cell density, temperature) anticipated for vaccine production. The inability of CAVA strains to replicate at 37 degrees C makes reversion to a neurovirulent phenotype in vivo highly unlikely, therefore, these strains can be considered safe for the manufacture of IPV. The CAVA strains were immunogenic in the Wistar rat potency model for cIPV, inducing high neutralizing antibody titers in a dose-dependent manner in response to D-antigen doses used for cIPV. In combinati

关键词： Vaccine hesitancy   Vaccine refusal   Social networks  

摘要： Objectives: Eradication and control of childhood diseases through immunization can only work if parents allow their children to be vaccinated. To learn about social network factors associated with polio vaccine hesitancy, we investigated social and spatial clustering of households by their vaccine acceptance status in Malegaon, India, an area known for vaccine refusal and repeated detection of polio cases. Methods: We interviewed family heads from 2462 households in 25 neighborhoods in July 2012 and constructed social networks based on advice seeking from other households. We restricted our main analyses to surveyed households for which we also had data on whether they accepted the polio vaccine for their eligible children or not. Results: Data from 2452 households was retained and these households made 2012 nominations to 830 households. Vaccine-refusing households had fewer outgoing ties than vaccine-accepting households. After excluding 24 isolated households, vaccine-refusing households had 189% more nominations to other vaccine-refusing households (93% more in the largest component of the network) compared to vaccine-accepting households, revealing that vaccine-refusing households cluster in the social network. Since roughly half of all ties connect households within neighborhoods, vaccine-refusing clusters lie in spatially localized "pockets". Conclusions: The social (and spatial) clustering of vaccine-refusing households could be leveraged to tailor communication strategies to improve vaccine acceptance and community perceptions of immunization programs for polio and other vaccine-preventable diseases. (C) 2016 Published by Elsevier Ltd.

关键词： VIRUS inactivation   VACCINATION   VACCINATION of infants   ORAL vaccines   RANDOMIZED controlled trials   POLIO vaccination   SAFETY measures  

摘要： Background Following the proposed worldwide switch from trivalent oral poliovirus vaccine (tOPV) to bivalent types 1 and 3 OPV (bOPV) in 2016, inactivated poliovirus vaccine (IPV) will be the only source of protection against poliovirus type 2. With most countries opting for one dose of IPV in routine immunisation schedules during this transition because of cost and manufacturing constraints, optimisation of protection against all poliovirus types will be a priority of the global eradication programme. We assessed the immunogenicity and safety of a novel monovalent high-dose inactivated poliovirus type 2 vaccine (mIPV2HD) in infants. Methods This observer-blind, comparative, randomised controlled trial was done in a single centre in Panama. We enrolled healthy infants who had not received any previous vaccination against poliovirus. Infants were randomly assigned (1:1) by computer-generated randomisation sequence to receive a single dose of either mIPV2HD or standard trivalent IPV given concurrently with a third dose of bOPV at 14 weeks of age. At 18 weeks, all infants were challenged with one dose of monovalent type 2 OPV (mOPV2). Primary endpoints were seroconversion and median antibody titres to type 2 poliovirus 4 weeks after vaccination with mIPV2HD or IPV;and safety (as determined by the proportion and nature of serious adverse events and important medical events for 8 weeks after vaccination). The primary immunogenicity analyses included all participants for whom a post-vaccination blood sample was available. All randomised participants were included in the safety analyses. This trial is registered with ***, number NCT02111135. Findings Between April 14 and May 9,2014,233 children were enrolled and randomly assigned to receive mIPV2HD (117 infants) or IPV (116 infants). 4 weeks after vaccination with mIPV2HD or IPV, seroconversion to poliovirus type 2 was recorded in 107 (93.0%, 95% CI 86.8-96.9) of 115 infants in the mIPV2HD group compared wit

关键词： Poliovirus   Poliomyelitis   Environmental surveillance   Polio eradication  

摘要： Wild polioviruses still remain endemic in three countries (Afghanistan, Pakistan, and Nigeria) and re-emergency of wild polio has been reported in previously polio-free countries. Environmental surveillance has been used as a supplementary tool in monitoring the circulation of wild poliovirus (PVs) and/or vaccine-derived PVs even in the absence of acute flaccid paralysis cases. This study aimed to monitor the presence of polioviruses in wastewater samples collected at one wastewater treatment plant located in the municipality of Rio de Janeiro, Brazil. From December 2011 to June 2012 and from September to December 2012, 31 samples were collected and processed. RD and L20B cell cultures were able to isolate PVs and non-polio enteroviruses in 27/31 samples. Polioviruses were isolated in eight samples (type 1 Sabin = 1, type 2 Sabin = 5, and type 3 Sabin = 2). Vaccine-derived polioviruses were not detected nor evidence of recombination with other PVs or non-polio enterovirus serotypes were observed among the isolates. The Sabin-related serotypes 2 and 3 presented nucleotide substitutions in positions associated with the neurovirulent phenotype at the 5'-UTR. Changes in important Amino acid residues at VP1 were also observed in the serotypes 2 and 3. Environmental surveillance has been used successfully in monitoring the circulation of PVs and non-polio enteroviruses and it is of crucial importance in the final stages of the WHO global polio eradication initiative. Our results show the continuous circulation of Sabin-like PVs and non-polio enteroviruses in the analyzed area during the study period.

摘要： Polio eradication is progressing rapidly, and the live attenuated Sabin strains in the oral poliovirus vaccine (OPV) are being removed sequentially, starting with type 2 in April 2016. For risk mitigation, countries are introducing inactivated poliovirus vaccine (IPV) into routine vaccination programs. After April 2016, monovalent type 2 OPV will be available for type 2 outbreak control. Because the current IPV is not suitable for house-to-house vaccination campaigns (the intramuscular injections require health professionals), we developed a high-density microprojection array, the Nanopatch, delivered monovalent type 2 IPV (IPV2) vaccine to the skin. To assess the immunogenicity of the Nanopatch, we performed a dose-matched study in rats, comparing the immunogenicity of IPV2 delivered by intramuscular injection or Nanopatch immunisation. A single dose of 0.2 D-antigen units of IPV2 elicited protective levels of poliovirus antibodies in 100% of animals. However, animals receiving IPV2 by IM required at least 3 immunisations to reach the same neutralising antibody titres. This level of dose reduction (1/40th of a full dose) is unprecedented for poliovirus vaccine delivery. The ease of administration coupled with the dose reduction observed in this study points to the Nanopatch as a potential tool for facilitating inexpensive IPV for mass vaccination campaigns.

关键词： POLIOVIRUS   PARALYSIS   IMMUNIZATION   INVESTIGATIONS   EPIDEMICS  

摘要： The article focuses on a study related to emergence of vaccine-derived polioviruses (VDVP) in several countries such as Ukraine and Myanmar from 2014-2015. Topics discussed include disease by vaccine-derived polioviruses such as paralysis; isolation of a VDPV which elicit a detailed outbreak investigation and local immunization response; and VDPV outbreak in Madagascar on September 29, 2014.

关键词： cell adhesion   cell permeabilization   intracellular trafficking   molecular biology   transferrin   blood brain barrier  

摘要： As a possible route for invasion of the CNS, circulating poliovirus (PV) in the blood is believed to traverse the blood-brain barrier (BBB), resulting in paralytic poliomyelitis. However, the underlying mechanism is poorly understood. In this study, we demonstrated that mouse transferrin receptor 1 (mTfR1) is responsible for PV attachment to the cell surface, allowing invasion into the CNS via the BBB. PV interacts with the apical domain of mTfR1 on mouse brain capillary endothelial cells (MBEC4) in a dose-dependent manner via its capsid protein (VP1). Wefound that F-G, G-H, and H-I loops in VP1 are important for this binding. However, C-D, D-E, and E-F loops in VP1-fused Venus proteins efficiently penetrate MBEC4 cells. These results imply that the VP1 functional domain responsible for cell attachment is different from that involved in viral permeation of the brain capillary endothelium. We observed that co-treatment of MBEC4 cells with excess PV particles but not dextran resulted in blockage of transferrin transport into cells. Using the Transwell in vitro BBB model, transferrin co-treatment inhibited permeation of PV into MBEC4 cells and delayed further viral permeation via mTfR1 knockdown. With mTfR1 as a positive mediator of PV-host cell attachment and PV permeation of MBEC4 cells, our results indicate a novel role of TfR1 as a cellular receptor for human PV receptor/CD155-independent PV invasion of the CNS.

关键词： Poliovirus   Herd immunity   Immune escape   Immunization   Vaccine   Seroprevalence  

摘要： In 2010, a type I poliovirus outbreak in Congo with 445 lethal cases was caused by a virus that was neutralized by sera of German adults vaccinated with inactivated polio vaccine with a reduced efficiency. This seroprevalence study was done in two cohorts immunized with other vaccination schedules. Russian children aged 3-6 years immunized with a combination of inactivated and live polio vaccines were reasonably well protected against any wild type poliovirus 1, including the Congolese isolate. Adults aged 20-29 years immunized only with live vaccine were apparently protected against the vaccine strain (92% seropositive), but only 50% had detectable antibodies against the Congo-2010 isolate. Both waning immunity and serological divergence of the Congolese virus could contribute to this result. (C) 2015 Elsevier B.V. All rights reserved.

关键词： 灭活脊灰疫苗   脊灰病毒   口服疫苗   肠道免疫   黏膜免疫   接种免疫   免疫应答   脊髓灰质炎病毒   脊髓灰质炎疫苗   肠道黏膜  

摘要： 背景：口服脊髓灰质炎病毒疫苗（OPV）诱发的肠道免疫并不完善,会随着时间的推移而减弱,而OPV也可以通过接种免疫的儿童进行传播。灭活脊髓灰质炎病毒疫苗（IPV）不引起肠道黏膜的免疫应答,但可以提高儿童通过之前接种OPV诱发的黏膜免疫的保护力。我们旨在评估IPV对于已接种OPV的儿童的肠道免疫的影响。