measles virus

麻疹病毒
  • 文章类型: Journal Article
    随着国家和地区朝着消除麻疹的方向发展,包括位于基质和融合蛋白基因之间的非编码区的扩展序列窗口(M-FNCR)被认为可用于分子监测。用2011-2018年在中国流行的192株基因型H1菌株评估了M-FNCR的分子分辨率。N450和M-FNCR目标的系统发育分析表明,这两个目标都可以确认与疫情有关的爆发,而M-FNCR靶标可以进一步提高分子表征的分辨率:(1)它可以区分在疾病发作后一个月内在一个县传播的具有相同N450的菌株;(2)可以区分具有相同N450的菌株的不同传播链;(3)在N450不一致的散发性病例中可以提供更好的时空拓扑一致性。因此,M-FNCR可用于补充来自N450的信息,以解决跟踪病毒传播链的具体问题。
    As countries and regions move toward measles elimination, extended sequence window including noncoding region located between the matrix and fusion protein genes (M - F NCR) was considered to be used in molecular surveillance. The molecular resolution of M - F NCR was evaluated with 192 genotype H1 strains circulating during 2011-2018 in China. Phylogenetic analyses of the N450 and M - F NCR targets indicated that both two targets could confirm epi-linked outbreak, while M - F NCR target could further improve resolution of the molecular characterization: (1) it could differentiate the strains with identical N450 circulated in one county within one month of disease onset; (2) different transmission chains could be distinguished for strains with identical N450; (3) better spatial-temporal consistency with topology could be provided among sporadic cases with inconsistent N450. Accordingly, M - F NCR could be used to complement the information from N450 to address the specific questions in tracking the virus transmission chains.
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  • 文章类型: Journal Article
    尽管广泛接种疫苗,麻疹仍然是对人类健康的主要威胁。虽然我们知道母体抗体会损害疫苗诱导的免疫力,预先存在的免疫水平的相对贡献,母婴对疫苗反应的特征仍不清楚,阻碍循证疫苗接种政策的制定。在这里,我们将母婴队列和儿童队列中的1,505名个体(0-12岁)的血清学数据与经验模型相结合,以重建出生时的抗体轨迹。我们表明,虽然在人群中存在高度异质性,麻疹抗体的进化从出生开始在个体水平上具有强烈的预测作用,包括接种疫苗。Further,我们发现剖腹产与2.56(95%置信区间:1.06-6.37)增加的主要疫苗失败的几率有关,强调出生途径的长期免疫学后果。最后,我们利用我们对抗体进化的新理解来批判性地评估不同疫苗接种时间表的人群水平后果,其结果将允许对疫苗政策进行国家一级的评估。
    Measles remains a major threat to human health despite widespread vaccination. While we know that maternal antibodies can impair vaccine-induced immunity, the relative contributions of pre-existing immunity levels, maternal and infant characteristics on vaccine responses remain unclear, hampering evidence-based vaccination policy development. Here we combine serological data from 1,505 individuals (aged 0-12 years) in a mother-infant cohort and in a child cohort with empirical models to reconstruct antibody trajectories from birth. We show that while highly heterogeneous across a population, measles antibody evolution is strongly predictive from birth at the individual level, including following vaccination. Further, we find that caesarean section births were linked with 2.56 (95% confidence interval: 1.06-6.37) increased odds of primary vaccine failure, highlighting the long-term immunological consequences of birth route. Finally, we use our new understanding of antibody evolution to critically assess the population-level consequences of different vaccination schedules, the results of which will allow country-level evaluations of vaccine policy.
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  • 文章类型: Journal Article
    随着SARS-CoV-2的持续发展和COVID-19病例在儿童和成人中迅速增加,迫切需要一种安全有效的疫苗,它能引起全身和粘膜体液免疫,以限制新变种的出现。以中国Hu191麻疹病毒(MeV-hu191)疫苗株为骨干,我们开发了稳定表达任一膜锚定融合前形式的MeV嵌合体,全长尖峰(rMeV-preFS),借助SARS-CoV-2OmicronBA.2的SP-D三聚标签(rMeV-SSPD)或其可溶性分泌的尖峰三聚体。通过鼻内或皮下途径在金色叙利亚仓鼠中施用两种疫苗候选物,以确定用于攻击的最佳免疫途径。rMeV-S+SPD的鼻内递送比皮下途径诱导更强烈的粘膜IgA抗体应答。rMeV-preFS通过鼻内常规诱导的粘膜IgA抗体略高于皮下途径,但没有显著差异。rMeV-preFS疫苗通过鼻内或皮下给药刺激比rMeV-S+SPD疫苗更高的粘膜IgA。在仓鼠中,rMeV-preFS疫苗的鼻内给药引起高水平的NAb,通过减少疫苗接种动物的病毒载量和减少病理变化来保护SARS-CoV-2OmicronBA.2变体攻击。令人鼓舞的是,从rMeV-preFS组收集的血清对最新变体XBB.1.16始终显示出稳健且显着高的中和滴度。这些数据表明,rMeV-preFS是一种非常有前途的COVID-19候选疫苗,具有开发成二价疫苗(MeV/SARS-CoV-2)的巨大潜力。
    As SARS-CoV-2 continues to evolve and COVID-19 cases rapidly increase among children and adults, there is an urgent need for a safe and effective vaccine that can elicit systemic and mucosal humoral immunity to limit the emergence of new variants. Using the Chinese Hu191 measles virus (MeV-hu191) vaccine strain as a backbone, we developed MeV chimeras stably expressing the prefusion forms of either membrane-anchored, full-length spike (rMeV-preFS), or its soluble secreted spike trimers with the help of the SP-D trimerization tag (rMeV-S+SPD) of SARS-CoV-2 Omicron BA.2. The two vaccine candidates were administrated in golden Syrian hamsters through the intranasal or subcutaneous routes to determine the optimal immunization route for challenge. The intranasal delivery of rMeV-S+SPD induced a more robust mucosal IgA antibody response than the subcutaneous route. The mucosal IgA antibody induced by rMeV-preFS through the intranasal routine was slightly higher than the subcutaneous route, but there was no significant difference. The rMeV-preFS vaccine stimulated higher mucosal IgA than the rMeV-S+SPD vaccine through intranasal or subcutaneous administration. In hamsters, intranasal administration of the rMeV-preFS vaccine elicited high levels of NAbs, protecting against the SARS-CoV-2 Omicron BA.2 variant challenge by reducing virus loads and diminishing pathological changes in vaccinated animals. Encouragingly, sera collected from the rMeV-preFS group consistently showed robust and significantly high neutralizing titers against the latest variant XBB.1.16. These data suggest that rMeV-preFS is a highly promising COVID-19 candidate vaccine that has great potential to be developed into bivalent vaccines (MeV/SARS-CoV-2).
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  • 文章类型: Journal Article
    背景:麻疹在巴基斯坦一直是一个重要的公共卫生问题,特别是在开伯尔-普赫图赫瓦省,零星和无声的流行病继续挑战现有的控制措施。本研究旨在评估KPK中麻疹病毒(MeV)的流行情况并调查其分子流行病学,并探讨可疑个体的疫苗接种状况。
    方法:在2021年2月至10月之间进行了一项横断面研究。使用酶联免疫吸附测定(ELISA)分析了来自研究人群的336例疑似麻疹病例的IgM抗体。从阳性病例的子集随机收集咽拭子进行分子分析。使用邻居连接方法进行MeV分离株的系统发育分析。还记录了个体的疫苗接种状况。
    结果:在可疑参与者中,61.0%(205/336)的IgM抗体ELISA阳性,男性(64.17%)的患病率高于女性(57.04%)。大多数病例(36.0%)在婴儿和幼儿中观察到,与以前的报告一致。大多数IgM阳性病例(71.7%)没有接种任何剂量的麻疹疫苗,强调疫苗覆盖率的差距和改进免疫计划的必要性。遗传分析表明,所有MeV分离株都属于B3基因型,与该地区以前报道的变异有微小的遗传变异。
    结论:这项研究为KPK中MeV的遗传流行病学提供了有价值的见解,巴基斯坦。未接种疫苗的人中麻疹感染的高发率凸显了提高对疫苗重要性的认识和加强常规免疫计划的紧迫性。
    BACKGROUND: Measles has been a significant public health concern in Pakistan, especially in the Khyber Pakhtunkhwa (KPK) province, where sporadic and silent epidemics continue to challenge existing control measures. This study aimed to estimate the prevalence and investigate the molecular epidemiology of the measles virus (MeV) in KPK and explore the vaccination status among the suspected individuals.
    METHODS: A cross-sectional study was conducted between February and October 2021. A total of 336 suspected measles cases from the study population were analyzed for IgM antibodies using Enzyme-Linked Immunosorbent Assay (ELISA). Throat swabs were randomly collected from a subset of positive cases for molecular analysis. Phylogenetic analysis of MeV isolates was performed using the neighbor-joining method. The vaccination status of individuals was also recorded.
    RESULTS: Among the suspected participants, 61.0% (205/336) were ELISA positive for IgM antibodies, with a higher prevalence in males (64.17%) compared to females (57.04%). The majority of cases (36.0%) were observed in infants and toddlers, consistent with previous reports. The majority of IgM-positive cases (71.7%) had not received any dose of measles vaccine, highlighting gaps in vaccine coverage and the need for improved immunization programs. Genetic analysis revealed that all MeV isolates belonged to the B3 genotype, with minor genetic variations from previously reported variants in the region.
    CONCLUSIONS: This study provides valuable insights into the genetic epidemiology of the MeV in KPK, Pakistan. The high incidence of measles infection among unvaccinated individuals highlights the urgency of raising awareness about vaccine importance and strengthening routine immunization programs.
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  • 文章类型: Journal Article
    母体抗体的减少可能导致婴儿在接受含麻疹疫苗(MCV)之前失去对麻疹的保护。本研究旨在探讨早产儿麻疹抗体(PT)的变化特点及影响因素,为优化目标人群MCV疫苗接种策略提供科学依据。在3、6和12个月的实际年龄(CA)从PT和足月婴儿(FT)收集血液样本。通过酶联免疫吸附法定量检测麻疹抗体。收集了人口统计学和疫苗接种信息。使用Kruskal-Wallis秩和检验比较不同孕龄(GA)组的麻疹抗体。并进行多元线性回归以确定抗体的相关因素。在接种MCV之前,PT的麻疹抗体随年龄的增加而显着降低。3、6月龄PT抗体阳性率分别为10.80%和3.30%,分别(p<.001)。12个月时,接受MCV疫苗接种的婴儿麻疹抗体和血清阳性率急剧增加(p<.001).回归分析表明,GA年龄越小或年龄越大,3个月时的抗体水平越低(p<.001,p=.018);而3个月及以上年龄的麻疹抗体水平越低,则6个月时的抗体水平越低(p<.001,p=.029)。由于MCV疫苗接种前母源抗体水平低,PT对麻疹易感。应考虑作出更多努力,在产后早期保护弱势群体。
    The waning of maternal antibodies may cause infants to lose protection against measles before receiving measles-containing vaccine (MCV). The aim of this study is to investigate the changing characteristics and influencing factors of measles antibodies in preterm infants (PT), and to provide scientific basis for optimizing MCV vaccination strategy of the target population. Blood samples were collected from PT and full-term infants (FT) at the chronological age (CA) of 3, 6, and 12 months. Measles antibodies were quantitatively detected by enzyme-linked immunosorbent assay. Demographic and vaccination information were both collected. Kruskal-Wallis rank sum test was used to compare the measles antibodies among different gestation age (GA) groups, and multiple linear regression was performed to identify the correlative factors for the antibodies. Measles antibodies of PT decreased significantly with age increasing before MCV vaccination. The positive rates of antibodies of PT were 10.80% and 3.30% at the age of 3 and 6 months, respectively (p < .001). At 12 months, the measles antibodies and seropositive rate in the infants who received MCV vaccination increased sharply (p < .001). Regression analyzes showed that the younger the GA or the older the age, the lower the antibodies at 3 months(p < .001,p = .018); while the lower measles antibody levels at 3 months and older age predicted the lower antibodies at 6 months(p < .001, p = .029). PT were susceptible to measles due to the low level of maternally derived antibodies before MCV vaccination. More efforts should be considered to protect the vulnerable population during their early postnatal life.
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  • 文章类型: Journal Article
    麻疹疫苗病毒株(MV-Edm)是开发有效溶瘤载体的潜在平台。然而,尽管临床前数据有希望,我们对影响MV-Edm感染和肿瘤内传播疗效的因素的理解,以及溶瘤病毒和与病毒感染相关的特定化学疗法之间的相互作用,仍然有限。因此,我们研究了Forskolin通过促进Rab27a依赖性囊泡转运系统来增强溶瘤MV-Edm的抗肿瘤作用的效力。用MV-Edm感染细胞后,我们观察到细胞质囊泡的积累增加。我们的研究表明,MV-Edm感染并在肿瘤中扩散,这是病毒溶瘤不可或缺的过程,依赖于肿瘤细胞的囊泡转运系统。尽管肿瘤细胞表现出通过下调Rab27a的表达来抑制MV-Edm扩散的反应机制,囊泡运输系统的关键成员,Rab27a的过表达促进了MV-Edm对A549肿瘤细胞的溶瘤功效。此外,我们发现Forskolin,Rab27a激动剂,能促进MV-Edm的体外溶瘤作用。我们的研究表明,在MV-Edm介导的溶瘤途径中,囊泡转运蛋白Rab27a可以促进MV-Edm感染细胞中MV-Edm的分泌和合胞体的生成。研究结果表明,Forskolin和MV-Edm的组合在体外发挥协同抗肿瘤作用,导致溶瘤升高。这一发现为肿瘤患者的临床治疗带来了希望。
    The measles vaccine virus strain (MV-Edm) serves as a potential platform for the development of effective oncolytic vectors. Nevertheless, despite promising pre-clinical data, our comprehension of the factors influencing the efficacy of MV-Edm infection and intratumoral spread, as well as the interactions between oncolytic viruses and specific chemotherapeutics associated with viral infection, remains limited. Therefore, we investigated the potency of Forskolin in enhancing the antitumor effect of oncolytic MV-Edm by promoting the Rab27a-dependent vesicular transport system. After infecting cells with MV-Edm, we observed an increased accumulation of cytoplasmic vesicles. Our study demonstrated that MV-Edm infection and spread in tumors, which are indispensable processes for viral oncolysis, depend on the vesicular transport system of tumor cells. Although tumor cells displayed a responsive mechanism to restrain the MV-Edm spread by down-regulating the expression of Rab27a, a key member of the vesicle transport system, over-expression of Rab27a promoted the oncolytic efficacy of MV-Edm towards A549 tumor cells. Additionally, we found that Forskolin, a Rab27a agonist, was capable of promoting the oncolytic effect of MV-Edm in vitro. Our study revealed that the vesicle transporter Rab27a could facilitate the secretion of MV-Edm and the generation of syncytial bodies in MV-Edm infected cells during the MV-Edm-mediated oncolysis pathway. The results of the study demonstrate that a combination of Forskolin and MV-Edm exerts a synergistic anti-tumor effect in vitro, leading to elevated oncolysis. This finding holds promise for the clinical treatment of patients with tumors.
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  • 文章类型: Journal Article
    麻疹,副粘病毒科和麻疹病毒属的成员,是一种由麻疹病毒引起的传染病,具有极强的传染性,可以通过接种疫苗预防。当麻疹患者咳嗽或打喷嚏时,病毒通过呼吸道飞沫传播。通常,病毒暴露后,麻疹症状的出现需要10-14d。结膜炎,高温,咳嗽,流鼻涕,和一个独特的皮疹是一些症状。尽管有麻疹疫苗接种,它仍然在世界范围内广泛传播。为了根除麻疹,再现数(即R0<1)必须保持小于1。这项研究使用双倍剂量的疫苗来模拟麻疹爆发,研究了Caputo意义上的SEIVR隔室模型。再现数R0和模型属性都被彻底检查。对于R0小于和大于1,可以确定所提出模型的局部和全局稳定性。为了实现模型的全局稳定性,使用Lyapunov函数,同时证明了所提出模型的存在性和唯一性。还获得了R0的前向灵敏度指数。对所提出的分数阶(FO)卡普托模型进行了模拟,以分析其图形表示和FO导数的重要性,以说明我们的理论发现如何产生影响。图形结果表明,通过增加疫苗剂量率,减少了麻疹的爆发。
    Measles, a member of the Paramyxoviridae family and the Morbillivirus genus, is an infectious disease caused by the measles virus that is extremely contagious and can be prevented through vaccination. When a person with the measles coughs or sneezes, the virus is disseminated by respiratory droplets. Normally, the appearance of measles symptoms takes 10-14 d following viral exposure. Conjunctivitis, a high temperature, a cough, a runny nose, and a distinctive rash are some of the symptoms. Despite the measles vaccination being available, it is still widespread worldwide. To eradicate measles, the Reproduction Number (i.e. R0<1) must remain less than unity. This study examines a SEIVR compartmental model in the caputo sense using a double dose of vaccine to simulate the measles outbreak. The reproduction number R0 and model properties are both thoroughly examined. Both the local and global stabilities of the proposed model are determined for R0 less and greater than 1. To achieve the model\'s global stability, the Lyapunov function is used while the existence and uniqueness of the proposed model are demonstrated In addition to the calculated and fitted biological parameters, the forward sensitivity indices for R0 are also obtained. Simulations of the proposed fractional order (FO) caputo model are performed in order to analyse their graphical representations and the significance of FO derivatives to illustrate how our theoretical findings have an impact. The graphical results show that the measles outbreak is reduced by increasing vaccine dosage rates.
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  • 文章类型: Journal Article
    埃博拉病毒(EBOV)感染是人类出血热的原因,死亡率很高。需要预防和治疗干预的共同努力来应对高度可变的RNA病毒。他们的感染经常导致疫情爆发。这里,我们已经筛选了2P2I3D化学文库使用基于纳米荧光素酶的蛋白质互补测定(NPCA)和分离的两个化合物,破坏EBOV蛋白片段VP35IID与dsRNA结合蛋白PKR和PACT的N末端的相互作用,参与IFN应答和/或内在免疫,分别。这两种化合物抑制细胞培养物中的EBOV感染以及麻疹病毒(MV)的感染,而与IFN诱导无关。因此,我们认为这些化合物是通过恢复由PACT驱动的固有免疫来抗病毒的。鉴于PACT在哺乳动物中高度保守,我们的数据支持在其他物种中进一步测试这些化合物,以及对抗其他负义RNA病毒。
    Infection with Ebola virus (EBOV) is responsible for hemorrhagic fever in humans with a high mortality rate. Combined efforts of prevention and therapeutic intervention are required to tackle highly variable RNA viruses, whose infections often lead to outbreaks. Here, we have screened the 2P2I3D chemical library using a nanoluciferase-based protein complementation assay (NPCA) and isolated two compounds that disrupt the interaction of the EBOV protein fragment VP35IID with the N-terminus of the dsRNA-binding proteins PKR and PACT, involved in IFN response and/or intrinsic immunity, respectively. The two compounds inhibited EBOV infection in cell culture as well as infection by measles virus (MV) independently of IFN induction. Consequently, we propose that the compounds are antiviral by restoring intrinsic immunity driven by PACT. Given that PACT is highly conserved across mammals, our data support further testing of the compounds in other species, as well as against other negative-sense RNA viruses.
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  • 文章类型: Journal Article
    乳腺癌,不断发生的肿瘤,是女性死亡率的主要决定因素之一。使用针对乳腺癌的常规疗法已经进行了一些无效的尝试。对现有疗法的抗性和它们各自的衰弱副作用已经导致研究进入使用病毒治疗癌症的新时代。病毒疗法构成具有多种治疗活性机制的发展中的治疗方式,其中病毒可以直接溶瘤,并且可以表达转基因或诱导针对肿瘤细胞的宿主免疫应答。几种不同的含DNA和RNA的病毒已被考虑用于乳腺癌的病毒治疗,包括腺病毒,疱疹病毒,牛痘,呼肠孤病毒,新城疫病毒,麻疹病毒和水疱性口炎病毒。本文旨在总结针对乳腺恶性肿瘤的病毒治疗剂。关键科学评论概念:在这篇评论论文中,我们提出了一种使用多种转基因和药物的病毒组合治疗的新策略。这些重组病毒已经提供了针对人乳腺癌的治疗功效的证据。
    Breast cancer, an unceasingly occurring neoplasm, is one of the major determinants of mortality in women. Several ineffective attempts have been pursued using with conventional therapies against breast cancer. Resistance to existing therapies and their respective debilitating adverse effects have led research toward a new era of cancer treatment using viruses. Virotherapy constitutes a developing treatment modality with multiple mechanisms of therapeutic activity in which the viruses can be directly oncolyticand can express transgenes or induce host immune response against tumor cells. Several different DNA- and RNA-containing viruses have been considered for virotherapy of breast cancer including adenovirus, herpes virus, vaccinia, reovirus, Newcastle Disease virus, measles virus and vesicular stomatitis virus. This review aims to summarize the viro-therapeutical agents against breast malignancies. Key Scientific Concepts of Review: In this review paper, we proposed a new strategy to virus\'s combinatorial treatments using several kinds of transgenes and drugs. These recombinant viruses have provided evidence of treatment efficacy against human breast cancer.
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  • 文章类型: Journal Article
    背景:随着麻疹疫苗接种率的提高,麻疹感染已经转移到婴儿人群中。我们在母亲和婴儿中进行了一项血清流行病学随访研究,以评估疏府地区的麻疹血清阳性率和母亲麻疹抗体的持久性。2018年至2020年喀什。
    方法:从0、3、5、8、9和12月龄的母亲及其婴儿中获取母亲的静脉血和脐带血。使用酶联免疫吸附测定法定量测量麻疹抗体。我们分析了孕产妇和新生儿麻疹抗体之间的相关性,和抗体在婴儿出生后持续存在。
    结果:新生儿产妇总比率为2.38(95CI:2.05-2.71)。母亲和新生儿的麻疹抗体分别为438.93IU/mL(95CI:409.47-470.51IU/mL)和440.10IU/mL(95CI:410.82-471.48IU/mL),分别。新生儿麻疹抗体在出生后下降,然后从8个月大开始开始增加。
    结论:婴儿麻疹抗体水平在出生后逐渐下降,与母体麻疹抗体水平无关。应努力消除麻疹。
    BACKGROUND: As measles vaccination coverage has increased, measles infection has shifted to the population of infants. We conducted a follow-up seroepidemiological study among mothers and their infants to evaluate measles seroprevalence and the persistence of maternal measles antibody in Shufu, Kashgar from 2018 to 2020.
    METHODS: Maternal venous blood and cord blood was obtained among mothers and their infants at 0, 3, 5, 8, 9, and 12 months of age. An enzyme-linked immunosorbent assay was used for quantitative measurement of measles antibodies. We analyzed the correlation between maternal and neonatal measles antibodies, and antibodies persistence after infants were born.
    RESULTS: The overall neonatal maternal ratio was 2.38 (95%CI: 2.05-2.71). The measles antibodies for mothers and newborns were 438.93 IU/mL (95%CI: 409.47-470.51 IU/mL) and 440.10 IU/mL (95%CI: 410.82-471.48 IU/mL), respectively. Neonatal measles antibodies were dropping after birth and then beginning to increase starting at 8 months of age.
    CONCLUSIONS: Infant measles antibody levels progressively declined after birth regardless of maternal measles antibody levels. Efforts should be carried out to eliminate measles.
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