人呼吸道合胞病毒小疏水蛋白研究进展

人呼吸道合胞病毒是人呼吸道感染病原中的重要病原。SH蛋白是人呼吸道合胞病毒粒子表面的一种小分子糖蛋白,可形成五聚体的离子通道结构。SH蛋白是人呼吸道合胞病毒复制的非必需蛋白,但可以影响病毒融合蛋白介导的细胞融合,近年研究发现SH蛋白胞外区与血蓝蛋白形成的复合物可作为人呼吸道合胞病毒疫苗的抗原,产生的抗体在体内能清除病毒感染的细胞。本综述旨在对人呼吸道合胞病毒SH蛋白最新研究成果进行总结和讨论,并对未来针对SH蛋白的研究方向加以展望。     

呼吸道合胞病毒感染的动物模型

正人呼吸道合胞病毒(hRSV)是引起世界范围内婴儿呼吸系统疾病以及住院治疗的主要原因,并导致了成年人中的高发病率和老年群体的额外死亡。当前尚无获批疫苗或者有效的治疗药物。人呼吸道合胞病毒疫苗候选物正在被源源不断地开发出来,它们面向不同人群,防范人呼吸道合胞病毒感染的风险。人呼吸道合胞病毒的动物模型在人呼吸道合胞病毒疫苗候选物的临床前试验中扮演了重要角色,尽管有很多候选物在临床前研究中显示出了效     

加单磷酰类脂A佐剂的呼吸道合胞病毒病毒体疫苗的效力与安全性

<正>在婴儿以及免疫功能低下的成人和老人中,呼吸道合胞病毒感染仍然是一个严重的健康问题,没有有效的可利用的疫苗的原因是由于存在一些障碍:非复制性呼吸道合胞病毒疫苗可引起过度的Th2型应答,增强了疫苗接种者自然感染呼吸道合胞病毒而引起的呼吸系统疾病。作者以前发现含有Toll样受体4配体单磷酰类脂A的重组呼吸道合胞病毒病毒体可加强疫苗诱导的免疫应答,并且使免疫应答倾向于Th1型应答,也就不会引起呼吸系统疾病,由于黏膜免疫接种是诱导呼吸道合胞病毒特     

人呼吸道合胞病毒感染对机体Th17、Treg及其之间平衡作用的研究进展

人呼吸道合胞病毒感染是影响儿童和老年人健康的主要因素。诸多研究证实人呼吸道合胞病毒感染可引起机体内Th17、Treg产生变化,影响Th17/Treg之间的平衡,诱发机体病理损伤,导致疾病发生。深入研究人呼吸道合胞病毒感染对机体Th17、Treg及其之间平衡的作用,对理清人呼吸道合胞病毒潜在的发病机制,寻找具有治疗作用的潜在靶标和通路,进而对相关疫苗和药物的研发具有重要的促进作用。本文分别从Th17细胞、Treg细胞的分化和人呼吸道合胞病毒感染对机体Th17、Treg及其之间平衡的作用等方面进行综述,以期对人呼吸道合胞病毒如何作用于机体有一更深入地了解。     

呼吸道合胞病毒G蛋白的相关研究

呼吸道合胞病毒G蛋白介导病毒附着在宿主细胞表面,且具有亚型间抗原结构变异大的特点,其抗原变异推测是呼吸道合胞病毒逃避已存在免疫监视,引起反复感染的原因,了解G蛋白与免疫反应的关系对研制呼吸道合胞病毒亚单位疫苗,有效地防治该病毒感染具有重要意义。     

副流感病毒的研究进展

副流感病毒是一类有包膜的单股负链RNA病毒,属副黏病毒,是一种常见的易被忽略的呼吸道感染病原体,主要引起婴幼儿及儿童严重的下呼吸道感染,其致病性仅次于呼吸道合胞病毒(RSV).目前,对副流感病毒的感染,缺乏有效的治疗药物和病毒疫苗.因此,建立快速、敏感和特异的副流感病毒感染的诊断方法,研发新型抗病毒药物和安全有效的副流感病毒疫苗成为研究热点.本研究就副流感病毒的生物学特性、疫苗研究、防治及检测技术作一综述.     

呼吸道合胞病毒mRNA疫苗的研究进展

呼吸道合胞病毒(respiratory syncytial virus, RSV)是引起急性呼吸道感染的主要病原体之一,给婴幼儿和老年人带来了沉重的疾病负担。自福尔马林灭活呼吸道合胞病毒疫苗(FI-RSV)失败以来,RSV疫苗研究进展缓慢。但近年随着对RSV F蛋白(fusion protein, F)结构研究的不断深入,RSV的候选疫苗取得了快速进展,RSV的候选疫苗种类也逐渐增多,包括RSV mRNA疫苗、重组载体疫苗、亚单位疫苗、病毒样颗粒疫苗、减毒活疫苗和嵌合疫苗等。其中,RSV mRNA疫苗具有成本低、免疫原性强、生产工艺简单、研发周期短、安全性高和易于标准化生产等特点,适合应对新发传染性疾病的防控。现就RSV疫苗的研究现状、RSV mRNA疫苗发展历程及临床研究进展作一概述。     

婴幼儿呼吸道合胞病毒主动免疫的新进展

在婴幼儿中,呼吸道合胞病毒是最重要的呼吸道感染病毒之一。本文讨论该病毒候选疫苗的研制和开发,包括PFP-1、PFP-2和BBG2Na亚单位疫苗以及冷传代／热敏感突变株等。     

基于融合蛋白的呼吸道合胞病毒疫苗的研究进展

呼吸道合胞病毒(respiratory syncytial virus,RSV)是一种引起严重下呼吸道感染的病原体,易感人群为婴幼儿、老年人及免疫功能低下者。目前尚无有效的抗病毒药物和预防疫苗。RSV融合蛋白(fusion protein,F蛋白)具有高度保守性,其诱导的抗体可同时抑制A型和B型两个亚型的RSV感染。因此,以F蛋白作为靶抗原的RSV亚单位疫苗、颗粒样疫苗和病毒载体疫苗是目前研究的主要策略。现就基于F蛋白的RSV疫苗研究进展作一综述。     

呼吸道合胞病毒感染的免疫病理和疫苗的研究概况

人呼吸道合胞病毒（ＲＳＶ）是引起婴幼儿严重下呼吸道感染的主要病原,到目前为止,对其致病机理还不完全清楚,还没有安全有效的疫苗来进行预防接种。本文概述了ＲＳＶ感染的病理生理与免疫之间的关系,详细介绍了ＲＳＶ疫苗的发展情况,尤其是活疫苗的发展前景。     

人3型副流感病毒疫苗的研究进展

人3型副流感病毒是一种主要感染人类肺部上皮细胞的副黏病毒,可引起肺炎和支气管炎,在婴幼儿和免疫力低下的成人中有较高的发病率。经过多年的研究,对人3型副流感病毒疫苗的研究取得了重要的进展,但还没有有效的抗病毒药物和批准的疫苗上市。目前研究主要集中在减毒活疫苗及亚单位疫苗等,对人3型副流感病毒当前疫苗的研究情况做简要的综述。     

呼吸道合胞病毒疫苗研究进展

呼吸道合胞病毒(RSV)是引起婴幼儿支气管炎和肺炎的主要原因,并可致免疫缺陷病人显著发病和死亡,RSV疫苗已被WHO列为全球最优先发展的疫苗之一。经过几十年的研究,虽然取得了显著进展,但尚未有RSV疫苗上市。目前RSV疫苗的研究主要集中于亚单位疫苗、减毒活疫苗和DNA疫苗等,其中亚单位疫苗和减毒活疫苗被认为最有前途,已分别进行了的临床试验。     

Current progress on development of respiratory syncytial virus vaccine

Human respiratory syncytial virus (HRSV) is a major cause of upper and lower respiratory tract illness in infants and young children worldwide. Despite its importance as a respiratory pathogen, there is currently no licensed vaccine for prophylaxis of HRSV infection. There are several hurdles complicating the development of a RSV vaccine: 1) incomplete immunity to natural RSV infection leading to frequent re-infection, 2) immature immune system and maternal antibodies of newborn infants who are the primary subject population, and 3) imbalanced Th2-biased immune responses to certain vaccine candidates leading to exacerbated pulmonary disease. After the failure of an initial trial featuring formalin-inactivated virus as a RSV vaccine, more careful and deliberate efforts have been made towards the development of safe and effective RSV vaccines without vaccine-enhanced disease. A wide array of RSV vaccine strategies is being developed, including live-attenuated viruses, protein subunit-based, and vector-based candidates. Though licensed vaccines remain to be developed, our great efforts will lead us to reach the goal of attaining safe and effective RSV vaccines in the near future.     

呼吸道合胞病毒载体疫苗研究进展

人呼吸道合胞病毒(human respiratory syncytial virus, RSV)是引起婴幼儿下呼吸道感染的最重要的病毒病原,RSV载体疫苗可在人细胞内从头合成,形成的蛋白质构象与RSV自然感染后表达的完全相同,不会导致抗原表位的丧失或变化,形成的免疫力更利于抵抗随后的自然感染;经黏膜途径免疫不会产生疾病增强作用,且能突破母传抗体的干扰,因而受到广泛关注。对近年来RSV载体疫苗的研究进展进行了综述。     

Effects of Formalin-Inactivated Respiratory Syncytial Virus (FI-RSV) in the Perinatal Lamb Model of RSV

Respiratory syncytial virus (RSV) is the most frequent cause of bronchiolitis in infants and children worldwide. There are currently no licensed vaccines or effective antivirals. The lack of a vaccine is partly due to increased caution following the aftermath of a failed clinical trial of a formalin-inactivated RSV vaccine (FI-RSV) conducted in the 1960’s that led to enhanced disease, necessitating hospitalization of 80% of vaccine recipients and resulting in two fatalities. Perinatal lamb lungs are similar in size, structure and physiology to those of human infants and are susceptible to human strains of RSV that induce similar lesions as those observed in infected human infants. We sought to determine if perinatal lambs immunized with FI-RSV would develop key features of vaccine-enhanced disease. This was tested in colostrum-deprived lambs immunized at 3–5 days of age with FI-RSV followed two weeks later by RSV infection. The FI-RSV-vaccinated lambs exhibited several key features of RSV vaccine-enhanced disease, including reduced RSV titers in bronchoalveolar lavage fluid and lung, and increased infiltration of peribronchiolar and perivascular lymphocytes compared to lambs either undergoing an acute RSV infection or naïve controls; all features of RSV vaccine-enhanced disease. These results represent a first step proof-of-principle demonstration that the lamb can develop altered responses to RSV following FI-RSV vaccination. The lamb model may be useful for future mechanistic studies as well as the assessment of RSV vaccines designed for infants.     

Parainfluenza virus type 3 expressing the native or soluble fusion (F) Protein of Respiratory Syncytial Virus (RSV) confers protection from RSV infection in African green monkeys

Respiratory syncytial virus (RSV) causes respiratory disease in young children, the elderly, and immunocompromised individuals, often resulting in hospitalization and/or death. After more than 40 years of research, a Food and Drug Administration-approved vaccine for RSV is still not available. In this study, a chimeric bovine/human (b/h) parainfluenza virus type 3 (PIV3) expressing the human PIV3 (hPIV3) fusion (F) and hemagglutinin-neuraminidase (HN) proteins from an otherwise bovine PIV3 (bPIV3) genome was employed as a vector for RSV antigen expression with the aim of generating novel RSV vaccines. b/h PIV3 vaccine candidates expressing native or soluble RSV F proteins were evaluated for efficacy and immunogenicity in a nonhuman primate model. b/h PIV3 is suited for development of pediatric vaccines since bPIV3 had already been evaluated in clinical studies in 1- and 2-month-old infants and was found to be safe, immunogenic, and nontransmissible in a day care setting (Karron et al., Pediatr. Infect. Dis. J. 15:650-654, 1996; Lee et al., J. Infect. Dis. 184:909-913, 2001). African green monkeys immunized with b/h PIV3 expressing either the native or soluble RSV F protein were protected from challenge with wild-type RSV and produced RSV neutralizing and RSV F-protein specific immunoglobulin G serum antibodies. The PIV3-vectored RSV vaccines evaluated here further underscore the utility of this vector system for developing safe and immunogenic pediatric respiratory virus vaccines.     

Decrease in Formalin-Inactivated Respiratory Syncytial Virus (FI-RSV) Enhanced Disease with RSV G Glycoprotein Peptide Immunization in BALB/c Mice

Respiratory syncytial virus (RSV) is a high priority target for vaccine development. One concern in RSV vaccine development is that a non-live virus vaccine would predispose for enhanced disease similar to that seen with the formalin inactivated RSV (FI-RSV) vaccine. Since a mAb specific to RSV G protein can reduce pulmonary inflammation and eosinophilia seen after RSV infection of FI-RSV vaccinated mice, we hypothesized that RSV G peptides that induce antibodies with similar reactivity may limit enhanced disease after subunit or other non-live RSV vaccines. In support of this hypothesis, we show that FI-RSV vaccinated mice administered RSV G peptide vaccines had a significant reduction in enhanced disease after RSV challenge. These data support the importance of RSV G during infection to RSV disease pathogenesis and suggest that use of appropriately designed G peptide vaccines to reduce the risk of enhanced disease with non-live RSV vaccines merits further study.     

Respiratory Syncytial Virus Human Experimental Infection Model: Provenance,Production, and Sequence of Low-Passaged Memphis-37 Challenge Virus

Respiratory syncytial virus (RSV) is the leading cause of lower respiratory tract infections in children and is responsible for as many as 199,000 childhood deaths annually worldwide. To support the development of viral therapeutics and vaccines for RSV, a human adult experimental infection model has been established. In this report, we describe the provenance and sequence of RSV Memphis-37, the low-passage clinical isolate used for the model''s reproducible, safe, experimental infections of healthy, adult volunteers. The predicted amino acid sequences for major proteins of Memphis-37 are compared to nine other RSV A and B amino acid sequences to examine sites of vaccine, therapeutic, and pathophysiologic interest. Human T- cell epitope sequences previously defined by in vitro studies were observed to be closely matched between Memphis-37 and the laboratory strain RSV A2. Memphis-37 sequences provide baseline data with which to assess: (i) virus heterogeneity that may be evident following virus infection/transmission, (ii) the efficacy of candidate RSV vaccines and therapeutics in the experimental infection model, and (iii) the potential emergence of escape mutants as a consequence of experimental drug treatments. Memphis-37 is a valuable tool for pre-clinical research, and to expedite the clinical development of vaccines, therapeutic immunomodulatory agents, and other antiviral drug strategies for the protection of vulnerable populations against RSV disease.     

Development of mRNA vaccines against respiratory syncytial virus (RSV)

Respiratory syncytial virus (RSV) is a single-stranded negative-sense RNA virus that is the primary etiologic pathogen of bronchitis and pneumonia in infants and the elderly. Currently, no preventative vaccine has been approved for RSV infection. However, advances in the characterization, and structural resolution, of the RSV surface fusion glycoprotein have revolutionized RSV vaccine development by providing a new target for preventive interventions. In general, six different approaches have been adopted in the development of preventative RSV therapeutics, namely, particle-based vaccines, vector-based vaccines, live-attenuated or chimeric vaccines, subunit vaccines, mRNA vaccines, and monoclonal antibodies. Among these preventive interventions, MVA-BN-RSV, RSVpreF3, RSVpreF, Ad26. RSV.preF, nirsevimab, clesrovimab and mRNA-1345 is being tested in phase 3 clinical trials, and displays the most promising in infant or elderly populations. Accompanied by the huge success of mRNA vaccines in COVID-19, mRNA vaccines have been rapidly developed, with many having entered clinical studies, in which they have demonstrated encouraging results and acceptable safety profiles. In fact, Moderna has received FDA approval, granting fast-track designation for an investigational single-dose mRNA-1345 vaccine against RSV in adults over 60 years of age. Hence, mRNA vaccines may represent a new, more successful, chapter in the continued battle to develop effective preventative measures against RSV. This review discusses the structure, life cycle, and brief history of RSV, while also presenting the current advancements in RSV preventatives, with a focus on the latest progress in RSV mRNA vaccine development. Finally, future prospects for this field are presented.     

Immunogenicity of recombinant measles vaccine expressing fusion protein of respiratory syncytial virus in cynomolgus monkeys

Respiratory syncytial virus (RSV) is a common cause of respiratory infections in infants. Effective vaccines are currently being sought, but no vaccine is thus far available. In our previous study, recombinant AIK‐C measles vaccine expressing the RSV fusion protein (MVAIK/RSV/F) was developed and protective immunity against RSV demonstrated in cotton rats. In the present study, the immunogenicity and protective effects were investigated in three cynomolgus monkeys immunized with MVAIK/RSV/F. Neutralizing test antibodies against RSV were detected and no infectious virus was recovered from the lungs of monkeys immunized with MVAIK/RSV/F after challenge. MVAIK/RSV/F has the potential to inhibit RSV infection.