关键词： VLP   heat stable   poliovirus  

摘要： Poliomyelitis is a highly infectious disease caused by poliovirus (PV). It can result in paralysis and may be fatal. Integrated global immunization programs using live-attenuated oral (OPV) and/or inactivated (IPV) PV vaccines have systematically reduced its spread and paved the way for eradication. Immunization will continue posteradication to ensure against reintroduction of the disease, but there are biosafety concerns for both OPV and IPV. They could be addressed by the production and use of virus-free virus-like particle (VLP) vaccines that mimic the "empty" capsids (ECs) normally produced in viral infection. Although ECs are antigenically in-distinguishable from mature virus particles, they are less stable and readily convert into an alternative conformation unsuitable for vaccine purposes. Stabilized ECs, expressed recombinantly as VLPs, could be ideal candidate vaccines for a polio-free world. However, although genome-free PV ECs have been expressed as VLPs in a variety of systems, their inherent antigenic instability has proved a barrier to further development. In this study, we selected thermally stable ECs of type 1 PV (PV-1). The ECs are antigenically stable at temperatures above the conversion temperature of wild-type (wt) virions. We have identified mutations on the capsid surface and in internal networks that are responsible for EC stability. With reference to the capsid structure, we speculate on the roles of these residues in capsid stability and postulate that such stabilized VLPs could be used as novel vaccines. IMPORTANCE Poliomyelitis is a highly infectious disease caused by PV and is on the verge of eradication. There are biosafety concerns about reintroduction of the disease from current vaccines that require live virus for production. Recombinantly expressed virus-like particles (VLPs) could address these inherent problems. However, the genome-free capsids (ECs) of wt PV are unstable and readily change antigenicity to a form not suitable as a

关键词： decay   diseases   enteroviruses   environmental health   fomite transmission   indoor environments   mathematical modelling   viral persistence  

摘要： AimsThe goal of this study was to explore various models for describing viral persistence (infectivity) on fomites and identify the best fit models. Methods and ResultsThe persistence of poliovirus over time was studied on three different fomite materials: steel, cotton and plastic. Known concentrations of poliovirus type 1 were applied to the surface coupons in an indoor environment for various lengths of time. Viruses were recovered from the surfaces by vortexing in phosphate buffer. Seven different mathematical models of relative persistence over time were fit to the data, and the preferred model for each surface was selected based on the Bayesian information criterion. ConclusionsWhile the preferred model varied by fomite type, the virus showed a rapid initial decay on all of the fomite types, followed by a transition to a more gradual decay after about 4-8days. Estimates of the time for 99% reduction ranged from 81h for plastic to 143h for cotton. A 6log reduction of recoverable infectivity of poliovirus did not occur during the 3-week duration of the experiment for any of the fomites. Significance and Impact of the StudyIn protected indoor environments poliovirus can remain infective for weeks. The models identified by this study can be used in risk assessments to identify appropriate strategies for managing this risk.

关键词： 80S   VHH   cryo-electron microscopy   expanded virus   poliovirus   single-domain antibodies   three-dimensional structure  

摘要： By using cryo-electron microscopy, expanded 80S-like poliovirus virions (poliovirions) were visualized in complexes with four 80S-specific camelid VHHs (Nanobodies). In all four complexes, the VHHs bind to a site on the top surface of the capsid protein VP3, which is hidden in the native virus. Interestingly, although the four VHHs bind to the same site, the structures of the expanded virus differ in detail in each complex, suggesting that each of the Nanobodies has sampled a range of low-energy structures available to the expanded virion. By stabilizing unique structures of expanded virions, VHH binding permitted a more detailed view of the virus structure than was previously possible, leading to a better understanding of the expansion process that is a critical step in infection. It is now clear which polypeptide chains become disordered and which become rearranged. The higher resolution of these structures also revealed well-ordered conformations for the EF loop of VP2, the GH loop of VP3, and the N-terminal extensions of VP1 and VP2, which, in retrospect, were present in lower-resolution structures but not recognized. These structural observations help to explain preexisting mutational data and provide insights into several other stages of the poliovirus life cycle, including the mechanism of receptor-triggered virus expansion. IMPORTANCE When poliovirus infects a cell, it undergoes a change in its structure in order to pass RNA through its protein coat, but this altered state is short-lived and thus poorly understood. The structures of poliovirus bound to single-domain antibodies presented here capture the altered virus in what appear to be intermediate states. A careful analysis of these structures lets us better understand the molecular mechanism of infection and how these changes in the virus lead to productive-infection events.

关键词： IPV   Nigeria   Pakistan   epidemiology   immunization   inactivated poliovirus vaccine   mass campaign   polio   poliovirus   trivalent oral polio vaccine   vaccination   vaccine campaign   vaccines   viruses  

摘要： In 2014, inactivated poliovirus vaccine (IPV) campaigns were implemented in Nigeria and Pakistan after clinical trials showed that IPV boosts intestinal immunity in children previously given oral poliovirus vaccine (OPV). We estimated the effect of these campaigns by using surveillance data collected during January 2014 April 2016. In Nigeria, campaigns with IPV and trivalent OPV (tOPV) substantially reduced the incidence of poliomyelitis caused by circulating serotype-2 vaccine derived poliovirus (incidence rate ratio [IRR] 0.17 for 90 days after vs. 90 days before campaigns, 95% Cl 0.04-0.78) and the prevalence of virus in environmental samples (prevalence ratio [PR] 0.16, 95% CI 0.02-1.33). Campaigns with tOPV alone resulted in similar reductions (IRR 0.59, 95% Cl 0.18-1.97;PR 0.45, 95% Cl 0.21-0.95). In Pakistan, the effect of IPV+tOPV campaigns on wild-type poliovirus was not significant. Results suggest that administration of IPV alongside OPV can decrease poliovirus transmission if high vaccine coverage is achieved.

关键词： Affordable IPV   IPV dose sparing   Dose investigation   Aluminium hydroxide adjuvant  

摘要： Background: There is a demand of affordable IPV in the World. Statens Serum Institut (SSI) has developed three reduced dose IPV formulations adsorbed to aluminium hydroxide;1/3 IPV-Al, 1/5 IPV-Al and 1/10 IPV-Al SSI, and now report the results of the first investigations in humans. Methods: 240 Danish adolescents, aged 10-15 years, and childhood vaccinated with IPV were booster vaccinated with 1/3 IPV-Al, 1/5 IPV-Al, 1/10 IPV-Al or IPV Vaccine SSI. The booster effects (GMTRs) of the three IPV-Al SSI were compared to IPV Vaccine SSI, and evaluated for non-inferiority. Immunogenicity results: The pre-vaccination GMTs were similar across the groups;926 (type 1), 969 (type 2) and 846 (type 3) in the total trial population. The GMTRs by poliovirus type and IPV formulation were: Type 1: 17.0 (1/3 IPV-Al), 13.0 (1/5 IPV-Al), 7.1 (1/10 IPV-Al) and 42.2 (IPV Vaccine SSI). Type 2: 12.5 (1/3 IPV-AI), 13.1 (1/5 IPV-AI), 7.6 (1/10 IPV-A1) and 47.8 (IPV Vaccine SSI). Type 3: 14.5 (1/3 IPV-A1), 16.2 (1/5 IPV-Al), 8.9 (1/10 IPV-A1) and 62.4 (IPV Vaccine SSI Thus, the three IPV-Al formulations were highly immunogenic, but inferior to IPV Vaccine SSI, in this booster vaccination trial. Safety results: No SAE and no AE of severe intensity occurred. 59.2% of the subjects reported at least one AE. Injection site pain was the most frequent AE in all groups;from 24.6% to 43.3%. Injection site redness and swelling frequencies were < 5% in most and < 10% in all groups. The most frequent systemic AEs were fatigue (from 8.2% to 15.0%) and headache (from 15.0% to 28.3%). Most AEs were of mild intensity. In conclusion, the three IPV-Al SSI were safe in adolescents and the booster effects were satisfactory. (C) 2016 The Authors. Published by Elsevier Ltd.).

关键词： ENTEROVIRUSES   PICORNAVIRUSES  

关键词： inactivated poliovirus vaccine   IPV   fractional dose   boost   boosting   poliovirus  

摘要： Background. Fractional-dose administration of inactivated poliovirus vaccine (fIPV) could increase IPV affordability and stretch limited supplies. We assessed immune responses following fIPV administered intradermally, compared with full-dose IPV administered intramuscularly, among adults with a history of oral poliovirus vaccine (OPV) receipt. Methods. We conducted a randomized, controlled noninferiority trial in Cuba. fIPV or IPV were administered on days 0 and 28;serum was collected on days 0, 7, 28, and 56 for analysis by a neutralization assay. The primary end point was seroconversion or a >= 4-fold rise in antibody titer. The noninferiority limit was 10%. The secondary end point was safety, assessed by the number and intensity of adverse reactions. Results. A total of 503 of 534 enrolled participants (94.2%) completed all study requirements. Twenty-eight days after the first dose, 94.8%, 98.0%, and 98.0% of fIPV recipients had an immune response to poliovirus types 1, 2, and 3, respectively, compared with 98.1% (P = .06), 98.0% (P = 1.00), and 99.2% (P = .45) in the IPV arm. Noninferiority was achieved on days 7, 28, and 56 for all serotypes. No serious adverse events were reported. Conclusion. fIPV induced similar boosting immune responses, compared with full-dose IPV. This suggests that fIPV would be an effective strategy to boost population immunity in an outbreak situation.

关键词： Poliovirus   Sewage -- Analysis   Oral vaccines   Immunization  

摘要： The article discusses on the Sabin-like type 2 polioviruses detection in the sewage samples from Ahmedabad and Hyderabad in India that were collected from August-September 2016. Topics mentioned include the detection was made after the government stop the trivalent oral poliovirus vaccine (tOPV), the swith on the use of bivalent OPV, and the suggestion to immunization workers to be alert on tOPV vials.

关键词： 诺贝尔生理学或医学奖   封面人物   脊髓灰质炎病毒   博士学位   哈佛大学   密歇根州   儿童医院   生物学家  

摘要： 托马斯·哈克·韦勒（美国，1915—2008年），1954年诺贝尔生理学或医学奖获得者。韦勒，1915年出生于美国密歇根州安阿伯镇。中学毕业后进入密歇根大学医学院动物学系，后又转入病理学系，于21岁时获得学士学位。1940年，获哈佛大学医学博士学位。1946年，任波士顿儿童医院医学研究所副所长。从1948年开始，韦勒与大学时的导师、美国著名病毒学和微生物学家恩德斯，以及自己读研究生时的同窗罗宾斯一道，共同从事脊髓灰质炎病毒研究。

关键词： Antiviral drugs   health economics   mathematical modelling   polio   oral poliovirus vaccine  

摘要： If the world can successfully control all outbreaks of circulating vaccine-derived poliovirus that may occur soon after global oral poliovirus vaccine (OPV) cessation, then immunodeficiencyassociated vaccine-derived polioviruses (iVDPVs) from rare and mostly asymptomatic long-term excretors (defined as >= 6 months of excretion) will become the main source of potential poliovirus outbreaks for as long as iVDPV excretion continues. Using existing models of global iVDPV prevalence and global long-term poliovirus risk management, we explore the implications of uncertainties related to iVDPV risks, including the ability to identify asymptomatic iVDPV excretors to treat with polio antiviral drugs (PAVDs) and the transmissibility of iVDPVs. The expected benefits of expanded screening to identify and treat long-term iVDPV excretors with PAVDs range from US$0.7 to 1.5 billion with the identification of 25-90% of asymptomatic long-term iVDPV excretors, respectively. However, these estimates depend strongly on assumptions about the transmissibility of iVDPVs and model inputs affecting the global iVDPV prevalence. For example, the expected benefits may decrease to as low as US$260 million with the identification of 90% of asymptomatic iVDPV excretors if iVDPVs behave and transmit like partially reverted viruses instead of fully reverted viruses. Comprehensive screening for iVDPVs will reduce uncertainties and maximize the expected benefits of PAVD use.