关键词： human infectious diseases   lettuce chloroplast transformation   bioencapsulation   oral delivery   Polio viral protein 1   mucosal immunity  

摘要： To prevent vaccine-associated paralytic poliomyelitis, WHO recommended withdrawal of Oral Polio Vaccine (Serotype-2) and a single dose of Inactivated Poliovirus Vaccine (IPV). IPV however is expensive, requires cold chain, injections and offers limited intestinal mucosal immunity, essential to prevent polio reinfection in countries with open sewer system. To date, there is no virus-free and cold chain-free polio vaccine capable of inducing robust mucosal immunity. We report here a novel low-cost, cold chain/poliovirus-free, booster vaccine using poliovirus capsid protein (VP1, conserved in all serotypes) fused with cholera non-toxic B subunit (CTB) expressed in lettuce chloroplasts. PCR using unique primer sets confirmed site-specific integration of CTB-VP1 transgene cassettes. Absence of the native chloroplast genome in Southern blots confirmed homoplasmy. Codon optimization of the VP1 coding sequence enhanced its expression 9-15-fold in chloroplasts. GM1-ganglioside receptor-binding ELISA confirmed pentamer assembly of CTB-VP1 fusion protein, fulfilling a key requirement for oral antigen delivery through gut epithelium. Transmission Electron Microscope images and hydrodynamic radius analysis confirmed VP1-VLPs of 22.3 nm size. Mice primed with IPV and boosted three times with lyophilized plant cells expressing CTB-VP1co, formulated with plant-derived oral adjuvants, enhanced VP1-specific IgG1, VP1-IgA titres and neutralization (80%-100% seropositivity of Sabin-1, 2, 3). In contrast, IPV single dose resulted in VP1-IgG1 and negligible VP1-IgA titres, poor neutralization and seropositivity (<20%, <40% Sabin 1,2). Mice orally boosted with CTB-VP1co, without IPV priming, failed to produce any protective neutralizing antibody. Because global population is receiving IPV single dose, booster vaccine free of poliovirus or cold chain offers a timely low-cost solution to eradicate polio.

关键词： reemerging infectious disease   accidental release   biological   laboratory infections   containment   poliovirus   viruses   vaccine-preventable diseases   polio   poliomyelitis  

摘要： The Global Polio Eradication Initiative continues to make progress toward the eradication target. Indigenous wild poliovirus (WPV) type 2 was last detected in 1999, WPV type 3 was last detected in 2012, and over the past 2 years WPV type 1 has been detected only in parts of 2 countries (Afghanistan and Pakistan). Once the eradication of poliomyelitis is achieved, infectious and potentially infectious poliovirus materials retained in laboratories, vaccine production sites, and other storage facilities will continue to pose a risk for poliovirus reintroduction into communities. The recent breach in containment of WPV type 2 in an inactivated poliovirus vaccine manufacturing site in the Netherlands prompted this review, which summarizes information on facility-associated release of polioviruses into communities reported over >8 decades. Successful polio eradication requires the management of poliovirus containment posteradication to prevent the consequences of the reestablishment of poliovirus transmission.

摘要： Stretching a full dose of IPV to make five fractional doses seemed promising, supported by clinical data from the earliest days of IPV development and followed up in studies from India and elsewhere.3–5 However, the lead-up to the April, 2016, switch from the trivalent oral poliovirus vaccine to the bivalent (type 1 plus type 3) oral poliovirus vaccine and the concurrent introduction of a dose of IPV into routine immunisation programmes changed the focus of this area of work because of unexpected challenges faced by manufacturers to scale up production.6 Suddenly, fractional-dose IPV was the only option for urgently stretching restricted IPV *** available data from fractional IPV trials were re-analysed, summarised, and discussed at the IEAG.8,10 After due deliberations, the IEAG called for a policy change—adaption of a two-dose intradermal fractional IPV strategy for routine immunisation, first in the states that had not introduced IPV, followed by the states that had already introduced full-dose *** February, 2016, other countries have introduced intradermal fractional IPV, including Sri Lanka, Bangladesh, Nepal, and, more recently, Cuba and Ecuador.[...]issues remain with this strategy, including the programmatic difficulties of intradermal administration of fractional-dose IPV (although a needle-free jet injector system for intradermal administration was prequalified by WHO in 2018), the IPV vial size (fractional-dose IPV is only recommended for single-dose or five-dose vials), and the reluctance of IPV manufacturers to apply for a label change.[...]this strategy might not be suitable for countries with a weak health workforce or for those with a rigid regulatory environment for which the off-label use would be a concern (although such use is more common than previously assumed).14 The importance of the fractional-dose IPV strategy cannot be over-emphasised.

摘要： Background Intradermal administration of fractional inactivated poliovirus vaccine (fIPV) is a dose-sparing alternative to the intramuscular full dose. We aimed to compare the immunogenicity of two fIPV doses versus one IPV dose for routine immunisation, and also assessed the immunogenicity of an fIPV booster dose for an outbreak response. Methods We did an open-label, randomised, controlled, inequality, non-inferiority trial in two clinics in Dhaka, Bangladesh. Healthy infants were randomly assigned at 6 weeks to one of four groups:group A received IPV at age 14 weeks and IPV booster at age 22 weeks;group B received IPV at age 14 weeks and fIPV booster at age 22 weeks;group C received IPV at age 6 weeks and fIPV booster at age 22 weeks;and group D received fIPV at 6 weeks and 14 weeks and fIPV booster at age 22 weeks. IPV was administered by needle-syringe as an intramuscular full dose (0.5 mL), and fIPV was administered intradermally (0.1 mL of the IPV formulation was administered using the 0.1 mL HelmJect auto-disable syringe with a Helms intradermal adapter). Both IPV and fIPV were administered on the outer, upper right thigh of infants. The primary outcome was vaccine response to poliovirus types 1, 2, and 3 at age 22 weeks (routine immunisation) and age 26 weeks (outbreak response). Vaccine response was defined as seroconversion from seronegative (<1:8) at baseline to seropositive (>= 1:8) or four-fold increase in reciprocal antibody titres adjusted for maternal antibody decay and was assessed in the modified intention-to-treat population (infants who received polio vaccines per group assignment and polio antibody titre results to serotypes 1, 2, and 3 at 6, 22, 23, and 26 weeks of age). The non-inferiority margin was 12.5%. This trial is registered with ***, number NCT02847026. Findings Between Sept 1, 2016 and May 2, 2017, 1076 participants were randomly assigned and included in the modified intention-to-treat analysis:271 in Group A, 267 in g

关键词： Health journalists   Polio eradication   Polio vaccine   Vaccine acceptance   Vaccine hesitancy, vaccination campaigns  

摘要： Introduction: Pakistan is one of only three poliomyelitis-endemic countries in the world. Twelve wild poliovirus (WPV) cases were recorded in the country in 2018. Even though resistance to oral polio vaccine (OPV) has decreased over time, there are still pockets of communities, mostly ethnic Pakhtun living in the Khyber Pakhtunkhwa (KP) province, that resist OPV. Although local journalists may be important sources of health information, past studies have overlooked their role in this context. The purpose of this study was to examine Pakhtun health journalists' beliefs regarding OPV and their views of the barriers and facilitators that influence OPV acceptance or hesitancy in their communities. Methods: We recruited and interviewed 33 Pakhtun journalists covering health issues for diverse media outlets in high-risk districts for WPV of the KP province. The semi-structured interviews were translated, transcribed, and analyzed for themes. Results: The participants strongly supported OPV and advocated that children in their own families and communities get vaccinated against polio. At the same time, they felt that their communities faced more urgent health needs that were not addressed by the government. They identified barriers at the media organizational level operating against accurate coverage of OPV, including financial and time constraints, a lack of checks and balances, and limited health literacy. They regarded press releases issued by the officials associated with OPV campaigns as the main facilitators in the coverage of OPV. The participants perceived lack of community trust in the government, security concerns, and community members' religious beliefs as the major impediments to increase in uptake of OPV. Conclusion: Pakhtun health journalists have the potential to be important partners in national polio eradication initiatives. They should receive culturally sensitive training in local languages at appropriate literacy levels. We also suggest direct involvem

关键词： Non-poliovirus enteroviruses   Hand   Foot and mouth disease   Human host factors   autophagy   Cell cycle arrest  

摘要： Non-polio enteroviruses are emerging viruses known to cause outbreaks of polio-like infections in different parts of the world with several cases already reported in Asia Pacific, Europe and in United States of America. These outbreaks normally result in overstretching of health facilities as well as death in children under the age of five. Most of these infections are usually self-limiting except for the neurological complications associated with human enterovirus A 71 (EV-A71). The infection dynamics of these viruses have not been fully understood, with most inferences made from previous studies conducted with ***-poliovirus enteroviral infections are responsible for major outbreaks of hand, foot and mouth disease (HFMD) often associated with neurological complications and severe respiratory diseases. The myriad of disease presentations observed so far in children calls for an urgent need to fully elucidate the replication processes of these viruses. There are concerted efforts from different research groups to fully map out the role of human host factors in the replication cycle of these viral infections. Understanding the interaction between viral proteins and human host factors will unravel important insights on the lifecycle of this groups of *** review provides the latest update on the interplay between human host factors/processes and non-polio enteroviruses (NPEV). We focus on the interactions involved in viral attachment, entry, internalization, uncoating, replication, virion assembly and eventual egress of the NPEV from the infected cells. We emphasize on the virus- human host interplay and highlight existing knowledge gaps that needs further studies. Understanding the NPEV-human host factors interactions will be key in the design and development of vaccines as well as antivirals against enteroviral infections. Dissecting the role of human host factors during NPEV infection cycle will provide a clear picture of how NPEVs usurp the huma

关键词： polio   IPV   Sri Lanka  

摘要： Background. In July 2016, Sri Lanka replaced 1 intramuscular dose of inactivated poliovirus vaccine (IPV) with 2 doses of intradermal fractional-dose IPV (fIPV) in its routine immunization schedule. We carried out a survey of seroprevalence of antipolio antibodies in children who received 2 fIPV doses and compared it with those who received 1 full IPV dose. Methods. Children born between March and December 2016 were randomly selected from 3 Sri Lankan districts (Colombo, Badulla, and Anuradhapura). Serum samples were collected and tested for presence of neutralizing antibodies to poliovirus types 1, 2, and 3. Results. Seroprevalence of antipolio antibodies was 100% in all districts for poliovirus type 1 and poliovirus type 3;it ranged between 90% and 93% for poliovirus type 2 (PV2) in children who received 1 full IPV dose and between 78% and 100% in those receiving 2 fIPV doses (P = .22). The median reciprocal titers of anti-PV2 antibodies were similar in children who received full-dose IPV and those who received fIPV (1:64 vs 1:45, respectively;P = .11). Conclusions. Our study demonstrated not only that Sri Lanka succeeded in maintaining very high primary immunization coverage also but that it is feasible for a national immunization program to implement fIPV immunization and achieve high coverage with intradermal application. The seroprevalence of anti-PV2 antibodies did not decrease after the introduction of fIPV.

关键词： 脊髓灰质炎后综合征   肌肉萎缩   疲劳感   疼痛   神经电生理  

摘要： 目的 探讨脊髓灰质炎后综合征(PPS)的临床表现及电生理特征,以利于该病的诊断水平。方法 收集河北医科大学第二医院神经内科就诊的2例PPS患者的临床资料,分析该病的主要临床表现及电生理特点。结果 例1患者7岁时患脊髓灰质炎,遗留右下肢短小。60年后出现缓慢进展的左下肢无力,肌肉萎缩;例2患者3岁时患脊髓灰质炎,遗留双下肢屈曲畸形,脊柱向右侧弯曲。47年后出现双上肢进行性无力,肌肉萎缩,疼痛,疲乏等表现,2例患者肌电图检查均以轻收缩时运动单位电位时限增宽及电位波幅增高为主,安静状态下自发电位少见。结论 PPS是脊髓灰质炎发病后,临床症状稳定多年后再次出现缓慢进展的迟缓性瘫痪,肌电图主要表现为慢性的神经再生过程。

关键词： 脊髓灰质炎病毒   DEAE   Sepharose   FF   介质稳定性  

摘要： 目的观察离子交换纯化脊髓灰质炎病毒Ⅰ型Sabin株稳定性,以研究病毒纯化的回收率和质量控制。方法使用微载体培养Vero细胞和脊灰病毒Ⅰ型Sabin株,经过逐级过滤澄清和100K超滤膜浓缩,再经凝胶介质初步纯化后的病毒液,然后观察经过离子介质DEAE Sepharose FF层析纯化5批次的纯化效果。对每次纯化获得的病毒液测定D抗原、蛋白质含量、牛血清白蛋白含量、DNA残留量以评价其质量。结果凝胶纯化后的病毒液,经离子介质DEAE Sepharose FF纯化,其D抗原、蛋白质含量、牛血清白蛋白含量、DNA残留量和比活性的批间差异不显著(P>0.05)。结论离子介质DEAE Sepharose FF在一定批次内纯化脊灰病毒工艺稳定。