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International Journal of Biological... 2021Respiratory syncytial virus (RSV) is one of the most important viral pathogens causing respiratory tract infection in infants, the elderly and people with poor immune... (Review)
Review
Respiratory syncytial virus (RSV) is one of the most important viral pathogens causing respiratory tract infection in infants, the elderly and people with poor immune function, which causes a huge disease burden worldwide every year. It has been more than 60 years since RSV was discovered, and the palivizumab monoclonal antibody, the only approved specific treatment, is limited to use for passive immunoprophylaxis in high-risk infants; no other intervention has been approved to date. However, in the past decade, substantial progress has been made in characterizing the structure and function of RSV components, their interactions with host surface molecules, and the host innate and adaptive immune response to infection. In addition, basic and important findings have also piqued widespread interest among researchers and pharmaceutical companies searching for effective interventions for RSV infection. A large number of promising monoclonal antibodies and inhibitors have been screened, and new vaccine candidates have been designed for clinical evaluation. In this review, we first briefly introduce the structural composition, host cell surface receptors and life cycle of RSV virions. Then, we discuss the latest findings related to the pathogenesis of RSV. We also focus on the latest clinical progress in the prevention and treatment of RSV infection through the development of monoclonal antibodies, vaccines and small-molecule inhibitors. Finally, we look forward to the prospects and challenges of future RSV research and clinical intervention.
Topics: Antiviral Agents; Genome, Viral; Humans; Respiratory Syncytial Virus Infections; Respiratory Syncytial Virus, Human; Viral Vaccines
PubMed: 34671221
DOI: 10.7150/ijbs.64762 -
Viruses Sep 2022Since the initial identification of respiratory syncytial virus (RSV) in 1956, much has been learned about the epidemiological impact and clinical manifestations of RSV...
Since the initial identification of respiratory syncytial virus (RSV) in 1956, much has been learned about the epidemiological impact and clinical manifestations of RSV infections [...].
Topics: Humans; Respiratory Syncytial Virus, Human; Respiratory Syncytial Virus Infections; Respiratory Tract Infections
PubMed: 36298665
DOI: 10.3390/v14102110 -
Viruses Oct 2022It is important to understand the features affecting virus replication, fitness, and transmissibility as they contribute to the outcome of infection and affect disease... (Review)
Review
It is important to understand the features affecting virus replication, fitness, and transmissibility as they contribute to the outcome of infection and affect disease intervention approaches. Respiratory syncytial virus (RSV) is a major contributor to respiratory disease, particularly in the infant and elderly populations. Although first described over 60 years ago, there are no approved vaccines and there are limited specific antiviral treatments due in part to our incomplete understanding of the features affecting RSV replication, immunity, and disease. RSV studies have typically focused on using continuous cell lines and conventional RSV strains to establish vaccine development and various antiviral countermeasures. This review outlines how the RSV G protein influences viral features, including replication, transmission, and disease, and how understanding the role of the G protein can improve the understanding of preclinical studies.
Topics: Infant; Humans; Aged; Respiratory Syncytial Virus Vaccines; Respiratory Syncytial Virus Infections; Respiratory Syncytial Virus, Human; Antiviral Agents; GTP-Binding Proteins; Antibodies, Viral
PubMed: 36366494
DOI: 10.3390/v14112396 -
Viruses Sep 2023Respiratory syncytial virus (RSV) infections are a constant public health problem, especially in infants and older adults. Virtually all children will have been infected... (Review)
Review
Respiratory syncytial virus (RSV) infections are a constant public health problem, especially in infants and older adults. Virtually all children will have been infected with RSV by the age of two, and reinfections are common throughout life. Since antigenic variation, which is frequently observed among other respiratory viruses such as SARS-CoV-2 or influenza viruses, can only be observed for RSV to a limited extent, reinfections may result from short-term or incomplete immunity. After decades of research, two RSV vaccines were approved to prevent lower respiratory tract infections in older adults. Recently, the FDA approved a vaccine for active vaccination of pregnant women to prevent severe RSV disease in infants during their first RSV season. This review focuses on the host response to RSV infections mediated by epithelial cells as the first physical barrier, followed by responses of the innate and adaptive immune systems. We address possible RSV-mediated immunomodulatory and pathogenic mechanisms during infections and discuss the current vaccine candidates and alternative treatment options.
Topics: Infant; Child; Female; Pregnancy; Humans; Aged; Respiratory Syncytial Virus Infections; Reinfection; Respiratory Syncytial Viruses; Immunity; Vaccines; Respiratory Syncytial Virus Vaccines; Respiratory Syncytial Virus, Human
PubMed: 37896776
DOI: 10.3390/v15101999 -
Vaccine Jul 2021Respiratory syncytial virus (RSV) is a leading cause of respiratory illness among children and infants worldwide, yet no licensed vaccine exists to reduce the risk of... (Review)
Review
Respiratory syncytial virus (RSV) is a leading cause of respiratory illness among children and infants worldwide, yet no licensed vaccine exists to reduce the risk of disease. At least 16 RSV vaccine candidates are currently in clinical development and many are designed to induce robust virus neutralizing immune responses. RSV neutralizing antibody (nAb)-mediated interventions such as intravenous immunoglobulin (IVIG) and palivizumab provide passive protection against serious lower respiratory tract disease due to RSV, validating nAbs as a correlate of protection. To identify correlates of protection for vaccine candidates that have demonstrated their protective efficacy, an investigator can use assays designed to measure nAb responses. However, there is no standard method of measurement; individual laboratories have developed their own methods to measure the ability of nAbs to reduce the infectivity of a defined virus dose in a variety of cell lines, leading to establishment of the broad variety of RSV neutralization assay formats currently in use. Standardizing the RSV neutralization assay is an essential step toward better assessment of nAb responses to vaccine candidates. Use of a common reference standard by all makes comparing the immunogenicity of different vaccine candidates feasible. In the context of vaccine development, the WHO 1 International Standard for Antiserum to RSV (RSV IS) has been shown to be suitable for harmonizing results across laboratories and assay formats used to measure nAb titers to RSV/A and RSV/B in human sera. This review describes the broad variety of RSV virus neutralization assay formats currently in use and the importance of the RSV IS for harmonization of results across formats and across laboratories. It also outlines good practices for key assay components and data analysis to promote the quality and consistency of measuring RSV nAb titers in serum specimens.
Topics: Antibodies, Neutralizing; Antibodies, Viral; Child; Humans; Immunity; Infant; Respiratory Syncytial Virus Infections; Respiratory Syncytial Virus Vaccines; Respiratory Syncytial Virus, Human
PubMed: 34244007
DOI: 10.1016/j.vaccine.2021.06.016 -
The Lancet. Respiratory Medicine Apr 2023Respiratory syncytial virus (RSV) is a major cause of hospitalisation in infants. The burden of RSV infection in healthy term infants has not yet been established.... (Observational Study)
Observational Study
BACKGROUND
Respiratory syncytial virus (RSV) is a major cause of hospitalisation in infants. The burden of RSV infection in healthy term infants has not yet been established. Accurate health-care burden data in healthy infants are necessary to determine RSV immunisation policy when RSV immunisation becomes available.
METHODS
We performed a multicentre, prospective, observational birth cohort study in healthy term-born infants (≥37 weeks of gestation) in five sites located in different European countries to determine the health-care burden of RSV. The incidence of RSV-associated hospitalisations in the first year of life was determined by parental questionnaires and hospital chart reviews. We performed active RSV surveillance in a nested cohort to determine the incidence of medically attended RSV infections. The study is registered with ClinicalTrials.gov, NCT03627572.
FINDINGS
In total, 9154 infants born between July 1, 2017, and April 1, 2020, were followed up during the first year of life and 993 participated in the nested active surveillance cohort. The incidence of RSV-associated hospitalisations in the total cohort was 1·8% (95% CI 1·6-2·1). There were eight paediatric intensive care unit admissions, corresponding to 5·5% of 145 RSV-associated hospitalisations and 0·09% of the total cohort. Incidence of RSV infection in the active surveillance cohort confirmed by any diagnostic assay was 26·2% (24·0-28·6) and that of medically attended RSV infection was 14·1% (12·3-16·0).
INTERPRETATION
RSV-associated acute respiratory infection causes substantial morbidity, leading to the hospitalisation of one in every 56 healthy term-born infants in high-income settings. Immunisation of pregnant women or healthy term-born infants during their first winter season could have a major effect on the health-care burden caused by RSV infections.
FUNDING
Innovative Medicines Initiative 2 Joint Undertaking, with support from the EU's Horizon 2020 research and innovation programme and European Federation of Pharmaceutical Industries and Associations.
Topics: Child; Female; Humans; Infant; Pregnancy; Cohort Studies; Europe; Hospitalization; Prospective Studies; Respiratory Syncytial Virus Infections; Respiratory Syncytial Virus, Human
PubMed: 36372082
DOI: 10.1016/S2213-2600(22)00414-3 -
Lancet (London, England) Apr 2022
Topics: Adenoviridae; COVID-19; Coinfection; Humans; Influenza, Human; Respiratory Syncytial Virus, Human; SARS-CoV-2
PubMed: 35344735
DOI: 10.1016/S0140-6736(22)00383-X -
Ugeskrift For Laeger Mar 2024Respiratory syncytial virus (RSV is) a common respiratory virus responsible for considerable morbidity and mortality among infants, elderly with comorbidity, and...
Respiratory syncytial virus (RSV is) a common respiratory virus responsible for considerable morbidity and mortality among infants, elderly with comorbidity, and immunocompromised adults. Two vaccines, Abrysvo and Arexvy, have been approved for prevention of severe RSV infection in adults ≥ 60 years of age. In addition, Abrysvo is approved for use during pregnancy to protect infants from RSV-associated lower respiratory tract infection. Currently, there is no national recommendation for the use of the vaccines, but vaccination of elderly at highest risk of severe RSV infection should be considered in a shared clinical decision making.
Topics: Infant; Adult; Pregnancy; Female; Humans; Aged; Respiratory Syncytial Virus Infections; Respiratory Syncytial Virus Vaccines; Respiratory Syncytial Virus, Human; Viral Vaccines
PubMed: 38533866
DOI: 10.61409/V12230800 -
Science Translational Medicine Aug 2023The RSVPreF3-AS01 vaccine, containing the respiratory syncytial virus (RSV) prefusion F protein and the AS01 adjuvant, was previously shown to boost neutralization...
The RSVPreF3-AS01 vaccine, containing the respiratory syncytial virus (RSV) prefusion F protein and the AS01 adjuvant, was previously shown to boost neutralization responses against historical RSV strains and to be efficacious in preventing RSV-associated lower respiratory tract diseases in older adults. Although RSV F is highly conserved, variation does exist between strains. Here, we characterized variations in the major viral antigenic sites among contemporary RSV sequences when compared with RSVPreF3 and showed that, in older adults, RSVPreF3-AS01 broadly boosts neutralization responses against currently dominant and antigenically distant RSV strains. RSV-neutralizing responses are thought to play a central role in preventing RSV infection. Therefore, the breadth of RSVPreF3-AS01-elicited neutralization responses may contribute to vaccine efficacy against contemporary RSV strains and those that may emerge in the future.
Topics: Humans; Aged; Respiratory Syncytial Viruses; Respiratory Syncytial Virus Infections; Vaccines; Antigens, Viral
PubMed: 37611082
DOI: 10.1126/scitranslmed.adg6050 -
Paediatric Drugs Nov 2023Pfizer is developing a bivalent respiratory syncytial virus (RSV) prefusion F subunit vaccine (RSVpreF; ABRYSVO™) for preventing RSV illness in infants and individuals... (Review)
Review
Pfizer is developing a bivalent respiratory syncytial virus (RSV) prefusion F subunit vaccine (RSVpreF; ABRYSVO™) for preventing RSV illness in infants and individuals aged ≥ 60 years. RSVpreF received approval for vaccination of pregnant individuals to help protect infants against RSV illness on 21 August 2023 in the USA. RSVpreF is also approved in the USA (31 May 2023) for active immunization of individuals aged ≥ 60 years for the prevention of lower respiratory tract disease (LRTD) caused by RSV. In the EU, RSVpreF has received approval for both indications, and it has been submitted for regulatory approval in Canada (both indications) and in Japan (maternal immunization to protect infants). This article summarizes the milestones in the development of RSVpreF leading to the approval for use in pregnant individuals to prevent LRTD in infants.
Topics: Female; Pregnancy; Humans; Infant; Respiratory Syncytial Virus Vaccines; Antibodies, Viral; Viral Fusion Proteins; Respiratory Syncytial Virus Infections; Respiratory Syncytial Viruses; Vaccines, Subunit
PubMed: 37831328
DOI: 10.1007/s40272-023-00598-3