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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 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 -
The Journal of Infectious Diseases Mar 2023The aim of this study was to investigate safety and immunogenicity of vaccine formulations against respiratory syncytial virus (RSV) containing the stabilized prefusion... (Randomized Controlled Trial)
Randomized Controlled Trial
BACKGROUND
The aim of this study was to investigate safety and immunogenicity of vaccine formulations against respiratory syncytial virus (RSV) containing the stabilized prefusion conformation of RSV fusion protein (RSVPreF3).
METHODS
This phase 1/2, randomized controlled, observer-blind study enrolled 48 young adults (YAs; aged 18-40 years) and 1005 older adults (OAs; aged 60-80 years) between January and August 2019. Participants were randomized into equally sized groups to receive 2 doses of unadjuvanted (YAs and OAs) or AS01-adjuvanted (OAs) vaccine or placebo 2 months apart. Vaccine safety and immunogenicity were assessed until 1 month (YAs) or 12 months (OAs) after second vaccination.
RESULTS
The RSVPreF3 vaccines boosted humoral (RSVPreF3-specific immunoglobulin G [IgG] and RSV-A neutralizing antibody) responses, which increased in an antigen concentration-dependent manner and were highest after dose 1. Compared to prevaccination, the geometric mean frequencies of polyfunctional CD4+ T cells increased after each dose and were significantly higher in adjuvanted than unadjuvanted vaccinees. Postvaccination immune responses persisted until end of follow-up. Solicited adverse events were mostly mild to moderate and transient. Despite a higher observed reactogenicity of AS01-containing vaccines, no safety concerns were identified for any assessed formulation.
CONCLUSIONS
Based on safety and immunogenicity profiles, the AS01E-adjuvanted vaccine containing 120 μg of RSVPreF3 was selected for further clinical development.
CLINICAL TRIALS REGISTRATION
NCT03814590.
Topics: Young Adult; Humans; Aged; Respiratory Syncytial Virus Vaccines; Antibodies, Viral; Respiratory Syncytial Virus Infections; Antibodies, Neutralizing; Respiratory Syncytial Virus, Human; Immunogenicity, Vaccine
PubMed: 35904987
DOI: 10.1093/infdis/jiac327 -
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 -
Annals of Allergy, Asthma & Immunology... Jul 2020The high burden associated with respiratory syncytial virus (RSV) has made the development of RSV vaccine(s) a global health high priority. This review summarizes the... (Review)
Review
OBJECTIVE
The high burden associated with respiratory syncytial virus (RSV) has made the development of RSV vaccine(s) a global health high priority. This review summarizes the journey to an RSV vaccine, the different strategies and challenges associated with the development of preventive strategies for RSV, and the diverse products that are undergoing clinical testing.
DATA SOURCES
Studies on RSV biology, immunology, epidemiology, and monoclonal antibodies (mAbs) and vaccines were searched using MEDLINE. We also searched PATH.org and ClinicalTrials.gov for updated information regarding the status of RSV vaccines and mAbs undergoing clinical trials.
STUDY SELECTIONS
We selected relevant studies conducted in infants and young children, pregnant women, and elderly population for the prevention of RSV infection.
RESULTS
Identification of a safe and immunogenic vaccine has been an important but elusive initiative for more than 60 years for different reasons, including the legacy of formalin-inactivated vaccine, our limited understanding of the immune response to RSV and how it relates to clinical disease severity, or the need for different end points according to the different vaccine platforms. Nevertheless, there are currently 39 vaccines and mAbs under development and 19 undergoing clinical trials.
CONCLUSION
Over the past decade, there have been significant advances in our knowledge of RSV molecular and structural biology and in understanding the human immune response to RSV. Despite the barriers, there are several promising mAbs and RSV vaccines undergoing clinical trials that hope to offer protection to the most vulnerable populations.
Topics: Female; Humans; Male; Respiratory Syncytial Virus Infections; Respiratory Syncytial Virus Vaccines; Respiratory Syncytial Virus, Human
PubMed: 32217187
DOI: 10.1016/j.anai.2020.03.017 -
Influenza and Other Respiratory Viruses Jan 2023Respiratory syncytial virus (RSV)-associated acute respiratory infection (ARI) is an underrecognized cause of illness in older adults. We conducted a systematic... (Meta-Analysis)
Meta-Analysis
BACKGROUND
Respiratory syncytial virus (RSV)-associated acute respiratory infection (ARI) is an underrecognized cause of illness in older adults. We conducted a systematic literature review and meta-analysis to estimate the RSV disease burden in adults ≥60 years in high-income countries.
METHODS
Data on RSV-ARI and hospitalization attack rates and in-hospital case fatality rates (hCFR) in adults ≥60 years from the United States, Canada, European countries, Japan, and South Korea were collected based on a systematic literature search (January 1, 2000-November 3, 2021) or via other methods (citation search, unpublished studies cited by a previous meta-analysis, gray literature, and an RSV-specific abstract booklet). A random effects meta-analysis was performed on estimates from the included studies.
RESULTS
Twenty-one studies were included in the meta-analysis. The pooled estimates were 1.62% (95% confidence interval [CI]: 0.84-3.08) for RSV-ARI attack rate, 0.15% (95% CI: 0.09-0.22) for hospitalization attack rate, and 7.13% (95% CI: 5.40-9.36) for hCFR. In 2019, this would translate into approximately 5.2 million cases, 470,000 hospitalizations, and 33,000 in-hospital deaths in ≥60-year-old adults in high-income countries.
CONCLUSIONS
RSV disease burden in adults aged ≥60 years in high-income countries is higher than previously estimated, highlighting the need for RSV prophylaxis in this age group.
Topics: Humans; Infant; Middle Aged; Aged; Developed Countries; Respiratory Syncytial Virus Infections; Respiratory Syncytial Virus, Human; Respiratory Tract Infections; Hospitalization; Cost of Illness
PubMed: 36369772
DOI: 10.1111/irv.13031 -
EMBO Molecular Medicine Apr 2022In virology, the term seasonality describes variations in virus prevalence at more or less regular intervals throughout the year. Specifically, it has long been...
In virology, the term seasonality describes variations in virus prevalence at more or less regular intervals throughout the year. Specifically, it has long been recognized that outbreaks of human influenza viruses, respiratory syncytial virus (RSV), and human coronaviruses occur in temperate climates during the winter season, whereas low activity is detected during the summer months. Other human respiratory viruses, such as parainfluenza viruses, human metapneumoviruses, and rhinoviruses, show highest activity during the spring or fall season in temperate regions, depending on the virus and subtype. In tropical climates, influenza viruses circulate throughout the year and no distinct seasonal patterns are observed, although virus outbreaks tend to spike during the rainy season. Overall, seasonality is more pronounced with greater distance from the equator, and tends to be less pronounced in regions closer to the equator (Li et al, 2019).
Topics: Humans; Influenza, Human; Metapneumovirus; Orthomyxoviridae; Respiratory Syncytial Virus Infections; Respiratory Syncytial Virus, Human; Respiratory Tract Infections; Viruses
PubMed: 35157360
DOI: 10.15252/emmm.202115352 -
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 -
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 -
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