Respiratory Syncytial Virus Vaccines

呼吸道合胞病毒疫苗
  • 文章类型: Systematic Review
    目的:确定呼吸道合胞病毒(RSV)疫苗在婴儿和老年人中的有效性和安全性。
    方法:我们对随机对照试验进行了系统评价和荟萃分析,这些试验评估了母体RSV免疫对婴儿感染的疗效。以及RSV疫苗在老年人中的功效。主要结果是针对RSV相关的下呼吸道疾病(LRTD)的疫苗功效。使用等级标准来评估证据水平。
    结果:本综述纳入了10项试验。对于孕产妇疫苗接种,RSV疫苗对RSV相关的LRTD表现出良好的疗效(疫苗效力57.3%,95%CI31.3至73.5;低确定性)和RSV相关的严重LRTD(疫苗疗效81.9%,95%CI56.8至92.4;中度确定性)出生后90天内的婴儿。对于老年人来说,Meta分析显示,RSV疫苗还可降低RSV相关LRTD的风险(疫苗效力78.3%,95%CI65.6至86.3;中等确定性)和RSV相关的严重LRTD(疫苗效力86.5%,95%CI68.3至94.3;中等确定性)。RSV疫苗和安慰剂之间的严重不良事件没有显着差异。
    结论:RSV疫苗有可能在婴儿和老年人中提供针对RSV疾病的保护。没有明显的安全问题。
    OBJECTIVE: To determine the efficacy and safety of respiratory syncytial virus (RSV) vaccines in infants and older adults.
    METHODS: We performed a systematic review and meta-analysis of randomized control trials that evaluated the efficacy of maternal RSV immunization against infections in infants, as well as the efficacy of RSV vaccines in older adults. The primary outcome was the vaccine efficacy against RSV-related lower respiratory tract disease (LRTD). Grading of Recommendations Assessment, Development and Evaluation criteria was used to evaluate the level of evidence.
    RESULTS: Ten trials were included in the review. For maternal vaccination, the RSV vaccine showed favourable efficacy against RSV-related LRTD (vaccine efficacy 57.3%, 95% confidence interval [CI] 31.3-73.5; low certainty) and RSV-related severe LRTD (vaccine efficacy 81.9%, 95% CI 56.8-92.4; moderate certainty) in infants within 90 days after birth. For older adults, Meta-analysis showed that RSV vaccines could also reduce the risk of RSV-related LRTD (vaccine efficacy 78.3%, 95% CI 65.6-86.3; moderate certainty) and RSV-related severe LRTD (vaccine efficacy 86.5%, 95% CI 68.3-94.3; moderate certainty). There was no significant difference in serious adverse events between RSV vaccines and placebo.
    CONCLUSIONS: RSV vaccines have the potential to offer protection against RSV disease in both infants and older adults, without apparent safety concerns.
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  • 文章类型: Journal Article
    目的:关于疗效的系统评价和荟萃分析存在显著的研究空白,免疫原性,呼吸道合胞病毒(RSV)预融合F疫苗的安全性。
    方法:我们对PubMed进行了全面搜索,Embase,Cochrane中央受控试验登记册,和ClinicalTrials.gov检索与功效相关的文章,免疫原性,RSV预融合F疫苗的安全性,发布至2023年9月8日。我们遵守系统审查和荟萃分析指南的首选报告项目。
    结果:本系统综述和荟萃分析共纳入22项随机对照试验,涉及78,990名参与者。RSV预融合F疫苗对RSV相关急性呼吸道疾病的疫苗有效性为68%(95%CI:59-75%),70%(95%CI:60-77%)与RSV相关的下呼吸道疾病,87%(95%CI:71-94%)针对医疗严重RSV相关下呼吸道疾病。RSV预融合F疫苗接种后常见的局部不良反应包括疼痛,发红,注射部位肿胀,和全身反应,如疲劳,头痛,肌痛,关节痛,恶心,和寒战。
    结论:我们的荟萃分析表明,使用RSV融合前F蛋白作为抗原的疫苗表现出广泛可接受的功效,免疫原性,和人口的安全。特别是,它提供了对严重RSV相关的下呼吸道疾病的高保护效率。
    OBJECTIVE: A notable research gap exists in the systematic review and meta-analysis concerning the efficacy, immunogenicity, and safety of the respiratory syncytial virus (RSV) prefusion F vaccine.
    METHODS: We conducted a comprehensive search across PubMed, Embase, the Cochrane Central Register of Controlled Trials, and ClinicalTrials.gov to retrieve articles related to the efficacy, immunogenicity, and safety of RSV prefusion F vaccines, published through September 8, 2023. We adhered to the Preferred Reporting Items for Systematic Reviews and Meta-Analyses guidelines.
    RESULTS: A total of 22 randomized controlled trials involving 78,990 participants were included in this systematic review and meta-analysis. The RSV prefusion F vaccine exhibited a vaccine effectiveness of 68% (95% CI: 59-75%) against RSV-associated acute respiratory illness, 70% (95% CI: 60-77%) against medically attended RSV-associated lower respiratory tract illness, and 87% (95% CI: 71-94%) against medically attended severe RSV-associated lower respiratory tract illness. Common reported local adverse reactions following RSV prefusion F vaccination include pain, redness, and swelling at the injection site, and systemic reactions such as fatigue, headache, myalgia, arthralgia, nausea, and chills.
    CONCLUSIONS: Our meta-analysis suggests that vaccines using the RSV prefusion F protein as antigen exhibit appears broadly acceptable efficacy, immunogenicity, and safety in the population. In particular, it provides high protective efficiency against severe RSV-associated lower respiratory tract disease.
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  • 文章类型: Journal Article
    呼吸道合胞病毒(RSV)是儿童急性下呼吸道感染的主要原因,对老年人构成重大风险。开发针对RSV的疫苗一直是当务之急,最近批准的Arexvy疫苗在预防60岁及以上人群中由RSV引起的下呼吸道疾病(LRTD)方面显示出希望。这篇全面的综述讨论了RSV的历史,疫苗开发中的挑战,以及Arexvy的作用机制。基于3期临床试验,探讨了疫苗的有效性和安全性。证明其在预防RSV相关LRTD方面的有效性。报告的最常见的不良反应包括注射部位疼痛,疲劳,肌痛,头痛,和关节痛.正在进行的研究集中在Arexvy的长期有效性,包括加强剂量的需要及其对减少RSV相关住院的影响。Arexvy减轻RSV相关疾病负担的潜力,特别是在弱势群体中,突出显示,强调广泛的免疫工作和获得这种开创性疫苗的重要性。
    The respiratory syncytial virus (RSV) is a major cause of acute lower respiratory tract infection in children and poses a significant risk to older adults. Developing a vaccine against RSV has been a priority, and the recently approved Arexvy vaccine has shown promise in preventing lower respiratory tract disease (LRTD) caused by RSV in individuals aged 60 years and older. This comprehensive review discusses the history of RSV, challenges in vaccine development, and the mechanism of action of Arexvy. The efficacy and safety of the vaccine are explored based on phase 3 clinical trial, demonstrating its effectiveness in preventing RSV-associated LRTD. The most common adverse reactions reported include injection site pain, fatigue, myalgia, headache, and arthralgia. Ongoing research focuses on the long-term effectiveness of Arexvy, including the need for booster doses and its impact on reducing RSV-associated hospitalizations. The potential of Arexvy to lessen the burden of RSV-related illnesses, particularly in vulnerable populations, is highlighted, emphasizing the importance of widespread immunization efforts and accessibility to this groundbreaking vaccine.
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  • 文章类型: Journal Article
    RSV is a leading cause of respiratory tract disease in infants and the elderly. RSV has limited therapeutic interventions and no FDA-approved vaccine. Gaps in our understanding of virus-host interactions and immunity contribute to the lack of biological countermeasures. This review updates the current understanding of RSV immunity and immunopathology with a focus on interferon responses, animal modeling, and correlates of protection.
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  • 文章类型: Journal Article
    信使RNA(mRNA)疫苗最近作为一种新型的疫苗技术出现,显示出对抗COVID-19大流行的强大潜力。除了引起大流行的SARS-CoV-2之外,已经开发并测试了mRNA疫苗,以预防由其他病毒引起的传染病,例如寨卡病毒,登革热病毒,呼吸道合胞病毒,流感H7N9和黄病毒。有趣的是,mRNA疫苗还可用于预防非感染性疾病如糖尿病和癌症。这篇综述总结了针对包括COVID-19在内的一系列疾病设计的mRNA疫苗的最新进展。由于表位研究是mRNA疫苗的计算机设计的主要组成部分,我们还调查了用于表位预测的先进生物信息学和机器学习算法,并审查可用于此目的的用户友好型软件工具。最后,我们讨论了一些关于mRNA疫苗的悬而未决的问题,比如未知的长期副作用,并提出我们对这个令人兴奋的领域未来发展的看法。
    Messenger RNA (mRNA) vaccines have recently emerged as a new type of vaccine technology, showing strong potential to combat the COVID-19 pandemic. In addition to SARS-CoV-2 which caused the pandemic, mRNA vaccines have been developed and tested to prevent infectious diseases caused by other viruses such as Zika virus, the dengue virus, the respiratory syncytial virus, influenza H7N9 and Flavivirus. Interestingly, mRNA vaccines may also be useful for preventing non-infectious diseases such as diabetes and cancer. This review summarises the current progresses of mRNA vaccines designed for a range of diseases including COVID-19. As epitope study is a primary component in the in silico design of mRNA vaccines, we also survey on advanced bioinformatics and machine learning algorithms which have been used for epitope prediction, and review on user-friendly software tools available for this purpose. Finally, we discuss some of the unanswered concerns about mRNA vaccines, such as unknown long-term side effects, and present with our perspectives on future developments in this exciting area.
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  • 文章类型: Journal Article
    Respiratory syncytial virus (RSV) is a leading cause of acute lower respiratory infection globally. There are vaccine candidates in development, but a systematic review on immunogenicity and safety of vaccine is lacking.
    This systematic review of RSV vaccine clinical trials was undertaken using four databases. Searches were conducted using both controlled vocabulary terms such as \"Respiratory Syncytial Virus, Human,\" \"Respiratory Syncytial Virus Infections,\" \"Respiratory Syncytial Virus Vaccines,\" \"Immunization,\" \"Immunization Programs\" and \"Vaccines\" and corresponding text word terms. The included studies were limited to clinical trials published from January 2000 to 31 December 2020. RSV infection case was defined as RSV-associated medically attended acute respiratory illness (MAARI) or RSV infection by serologically confirmed test (Western blot) during the RSV surveillance period. We calculated the relative risk of each vaccine trial with RSV infection case.
    Of 6306 publications, 38 were included and data were extracted covering four major types of RSV vaccine candidates, these being live-attenuated/chimeric (n = 14), recombinant-vector (n = 6), subunit (n = 12) and nanoparticle vaccines (n = 6). For RSV infection cases, nine trials were involved and none of them showed a vaccine-related increased MAARI during RSV surveillance season.
    LID ∆M2-2, MEDI M2-2, RSVcps2 and LID/∆M2-2 /1030s (live-attenuated) were considered the most promising vaccine candidates in infant and children. In the elderly, a nanoparticle F vaccine candidate and Ad26.RSV.preF were considered as two potential effective vaccines. A promising maternal vaccine candidate is still lacking.
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  • 文章类型: Journal Article
    Due to high burden of respiratory syncytial virus (RSV) in low- and middle-income countries (LMIC), international funding organizations have prioritized the development of RSV vaccines. Mathematical models of RSV will play an important role in assessing the relative value of these interventions. Our objectives were to provide an overview of the existing RSV modelling literature in LMIC and summarize available results on population-level effectiveness and cost-effectiveness.
    We searched MEDLINE from 2000 to 2020 for English language publications that employed a mathematical model of RSV calibrated to LMIC. Qualitative data were extracted on study and model characteristics. Quantitative data were collected on key model input assumptions and base case effectiveness and cost-effectiveness estimates for various immunization strategies.
    Of the 283 articles reviewed, 15 met inclusion criteria. Ten studies used modelling techniques to explore RSV transmission and/or natural history, while eight studies evaluated RSV vaccines and/or monoclonal antibodies, three of which included cost-effectiveness analyses. Six studies employed deterministic compartmental models, five studies employed individual transmission models, and four studies used different types of cohort models. Nearly every model was calibrated to at least one middle-income country, while four were calibrated to low-income countries.
    The mathematical modelling literature in LMIC has demonstrated the potential effectiveness of RSV vaccines and monoclonal antibodies. This review has demonstrated the importance of accounting for seasonality, social contact rates, immunity from prior infection and maternal antibody transfer. Future models should consider incorporating individual-level risk factors, subtype-specific effects, long-term sequelae of RSV infections, and out-of-hospital mortality.
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  • 文章类型: Research Support, Non-U.S. Gov\'t
    Several vaccine and antibody candidates are currently in development for the prevention of lower respiratory tract infections caused by the respiratory syncytial virus (RSV).
    We searched MEDLINE, Embase, and SCOPUS and included model-based evaluations of RSV vaccinations. Two reviewers performed the selection, data extraction, and quality evaluation with EVIDEM. Cost-effectiveness (CE) estimates were converted to $US purchasing power parity (PPP), year 2018 values. Potential economic and epidemiological outcomes were summarised for maternal, infant, children, and elderly vaccinations. The PROSPERO identifier is CRD42019122570.
    In total, 22 model-based studies were reviewed. On average, a potential 27% reduction in RSV hospitalisations in infants was projected for maternal vaccination and 50% for direct infant immunisation. The CE of maternal vaccination was $US1766-5857 PPP 2018/disability-adjusted life-years (DALYs) for Global Alliance for Vaccines and Immunisation (Gavi)-eligible countries. For England, the maximum cost-effective price of maternal vaccination was estimated at $US81.5 PPP 2018. Infant vaccination was associated with higher CE ratios in low- and high-income settings. Vaccination of neonates born before the RSV season was the most cost effective in high-income settings. Higher values for vaccine effectiveness, duration of protection, and vaccine uptake increased the benefits. Due to indirect effects, the vaccination of school-age children and a cocooning strategy were effective alternatives to protect infants, and the vaccination of children aged < 5 years had a beneficial impact on the elderly.
    RSV vaccines with anticipated characteristics may reduce a sizeable proportion of the RSV burden. The results are subject to uncertainty because of the limited epidemiological and clinical data. Data on RSV incidence and hospitalisation risk for granular age strata should be prioritised to facilitate the evaluation of RSV interventions and decision making.
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  • 文章类型: Consensus Development Conference
    原发性纤毛运动障碍(PCD)是一种遗传异质性,罕见的肺部疾病导致儿童和成人的慢性肺-肺-肺疾病。由于缺乏诊断测试方法的经验,许多医生错误地诊断PCD或从其鉴别诊断中消除PCD。到目前为止,所有用于PCD的疗法均未通过大型临床试验得到证实.这篇综述文章概述了北美PCD医生的共识建议,他们在过去10年中一直从事以PCD为中心的研究联盟。这些建议已被PCD基金会理事会采纳,为PCD临床中心提供诊断测试的指导,监测,以及PCD患者的短期和长期治疗方法。
    Primary ciliary dyskinesia (PCD) is a genetically heterogeneous, rare lung disease resulting in chronic oto-sino-pulmonary disease in both children and adults. Many physicians incorrectly diagnose PCD or eliminate PCD from their differential diagnosis due to inexperience with diagnostic testing methods. Thus far, all therapies used for PCD are unproven through large clinical trials. This review article outlines consensus recommendations from PCD physicians in North America who have been engaged in a PCD centered research consortium for the last 10 years. These recommendations have been adopted by the governing board of the PCD Foundation to provide guidance for PCD clinical centers for diagnostic testing, monitoring, and appropriate short and long-term therapeutics in PCD patients.
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  • 文章类型: Journal Article
    呼吸道合胞病毒(RSV)是儿童期最重要的病原性感染之一,并且与显著的发病率和死亡率相关。尽管已经对流行病学进行了广泛的研究,临床表现,诊断技术,动物模型和感染的免疫生物学,目前还没有令人信服和安全的疫苗。RSV感染的主要组织病理学特征是急性细支气管炎,粘膜和粘膜下水肿,和管腔阻塞脱落的上皮细胞与巨噬细胞混合的细胞碎片,纤维蛋白链,还有一些黏蛋白.有一个单一的RSV血清型与两个主要的抗原亚群,A和B两种亚型的菌株经常共同循环,但通常一种亚型占主导地位。在温带气候下,RSV感染反映出明显的季节性,在秋末或初冬发作。据信大多数儿童到2岁时将经历至少一种RSV感染。有几种关键的RSV动物模型。这些包括小鼠模型,更重要的是,牛模型;后者反映了与人类疾病的明显相似性。重要的是,在婴儿期或儿童早期因RSV住院的儿童中,哮喘的患病率明显较高.然而,对有可能解释这种易感性增加的候选基因的研究有限.特应性易感性似乎易患哮喘的后续发展,并且哮喘的后续发展可能继发于涉及细胞因子的致病性炎症反应。趋化因子及其同源受体。正在评估许多开发RSV疫苗的方法,以及使用较新的抗病毒药物来减轻疾病。同时感染的潜在影响和定义RSV的自然史也受到了极大的关注。显然,需要更多的研究来定义RSV毛细支气管炎之间的关系,其他病毒诱导的炎症反应,和哮喘。
    Respiratory syncytial virus (RSV) is amongst the most important pathogenic infections of childhood and is associated with significant morbidity and mortality. Although there have been extensive studies of epidemiology, clinical manifestations, diagnostic techniques, animal models and the immunobiology of infection, there is not yet a convincing and safe vaccine available. The major histopathologic characteristics of RSV infection are acute bronchiolitis, mucosal and submucosal edema, and luminal occlusion by cellular debris of sloughed epithelial cells mixed with macrophages, strands of fibrin, and some mucin. There is a single RSV serotype with two major antigenic subgroups, A and B. Strains of both subtypes often co-circulate, but usually one subtype predominates. In temperate climates, RSV infections reflect a distinct seasonality with onset in late fall or early winter. It is believed that most children will experience at least one RSV infection by the age of 2 years. There are several key animal models of RSV. These include a model in mice and, more importantly, a bovine model; the latter reflects distinct similarity to the human disease. Importantly, the prevalence of asthma is significantly higher amongst children who are hospitalized with RSV in infancy or early childhood. However, there have been only limited investigations of candidate genes that have the potential to explain this increase in susceptibility. An atopic predisposition appears to predispose to subsequent development of asthma and it is likely that subsequent development of asthma is secondary to the pathogenic inflammatory response involving cytokines, chemokines and their cognate receptors. Numerous approaches to the development of RSV vaccines are being evaluated, as are the use of newer antiviral agents to mitigate disease. There is also significant attention being placed on the potential impact of co-infection and defining the natural history of RSV. Clearly, more research is required to define the relationships between RSV bronchiolitis, other viral induced inflammatory responses, and asthma.
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