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Frontiers in Immunology 2023Respiratory syncytial virus (RSV) is a significant causative agent of bronchitis and pneumonia in infants and children. The identification and structural analysis of the... (Review)
Review
Respiratory syncytial virus (RSV) is a significant causative agent of bronchitis and pneumonia in infants and children. The identification and structural analysis of the surface fusion glycoprotein of RSV represents a pivotal advancement in the development of RSV prevention. This review provides a comprehensive summary of RSV monoclonal antibody (mAb) and vaccine clinical trials registered on ClinicalTrials.gov, emphasizing on the classification, name, target, phase, clinical outcomes, and safety data of RSV vaccination in newborns, infants and children. We also discuss the characteristics of the types of RSV vaccines for maternal immunity and summarize the current clinical research progress of RSV vaccination in pregnant women and their protective efficacy in infants. This review will provide new ideas for the development of RSV prevention for children in the future.
Topics: Humans; Infant, Newborn; Infant; Child; Female; Pregnancy; Pregnant Women; Respiratory Syncytial Virus Infections; Respiratory Syncytial Virus, Human; Respiratory Syncytial Virus Vaccines; Vaccination; Antibodies, Viral
PubMed: 38327765
DOI: 10.3389/fimmu.2023.1329426 -
Viruses Jan 2023With technological advancements enabling globalization, the intercontinental transmission of pathogens has become much easier. Respiratory viruses are one such group of... (Review)
Review
With technological advancements enabling globalization, the intercontinental transmission of pathogens has become much easier. Respiratory viruses are one such group of pathogens that require constant monitoring since their outbreak leads to massive public health crises, as exemplified by the influenza virus, respiratory syncytial virus (RSV), and the recent coronavirus disease 2019 (COVID-19) outbreak caused by the SARS-CoV-2. To prevent the transmission of these highly contagious viruses, developing prophylactic tools, such as vaccines, is of considerable interest to the scientific community. Virus-like particles (VLPs) are highly sought after as vaccine platforms for their safety and immunogenicity profiles. Although several VLP-based vaccines against hepatitis B and human papillomavirus have been approved for clinical use by the United States Food and Drug Administration, VLP vaccines against the three aforementioned respiratory viruses are lacking. Here, we summarize the most recent progress in pre-clinical and clinical VLP vaccine development. We also outline various strategies that contributed to improving the efficacy of vaccines against each virus and briefly discuss the stability aspect of VLPs that makes it a highly desired vaccine platform.
Topics: United States; Humans; Vaccines, Virus-Like Particle; COVID-19; SARS-CoV-2; Hepatitis B; Respiratory Syncytial Virus, Human
PubMed: 36851606
DOI: 10.3390/v15020392 -
International Journal of Molecular... Jan 2023In this review manuscript, we discuss the effects of select common viruses on insulin sensitivity and blood-brain barrier (BBB) function and the potential overlapping... (Review)
Review
In this review manuscript, we discuss the effects of select common viruses on insulin sensitivity and blood-brain barrier (BBB) function and the potential overlapping and distinct mechanisms involved in these effects. More specifically, we discuss the effects of human immunodeficiency virus (HIV), herpes, hepatitis, influenza, respiratory syncytial virus (RSV), and SARS-CoV-2 viruses on insulin sensitivity and BBB function and the proposed underlying mechanisms. These viruses differ in their ability to be transported across the BBB, disrupt the BBB, and/or alter the function of the BBB. For RSV and SARS-CoV-2, diabetes increases the risk of infection with the virus, in addition to viral infection increasing the risk for development of diabetes. For HIV and hepatitis C and E, enhanced TNF-a levels play a role in the detrimental effects. The winter of 2022-2023 has been labeled as a tridemic as influenza, RSV, and COVID-19 are all of concern during this flu season. There is an ongoing discussion about whether combined viral exposures of influenza, RSV, and COVID-19 have additive, synergistic, or interference effects. Therefore, increased efforts are warranted to determine how combined viral exposures affect insulin sensitivity and BBB function.
Topics: Humans; Influenza, Human; Respiratory Syncytial Virus Infections; Blood-Brain Barrier; Insulin Resistance; COVID-19; SARS-CoV-2; Respiratory Syncytial Virus, Human; HIV Infections
PubMed: 36768699
DOI: 10.3390/ijms24032377 -
Influenza and Other Respiratory Viruses Jan 2023External quality assessments (EQAs) for the molecular detection of human respiratory syncytial virus (RSV) are necessary to ensure the standardisation of reliable...
BACKGROUND
External quality assessments (EQAs) for the molecular detection of human respiratory syncytial virus (RSV) are necessary to ensure the standardisation of reliable results. The Phase II, 2019-2020 World Health Organization (WHO) RSV EQA included 28 laboratories in 26 countries. The EQA panel evaluated performance in the molecular detection and subtyping of RSV-A and RSV-B. This manuscript describes the preparation, distribution, and analysis of the 2019-2020 WHO RSV EQA.
METHODS
Panel isolates underwent whole genome sequencing and in silico primer matching. The final panel included nine contemporary, one historical virus and two negative controls. The EQA panel was manufactured and distributed by the UK National External Quality Assessment Service (UK NEQAS). National laboratories used WHO reference assays developed by the United States Centers for Disease Control and Prevention, an RSV subtyping assay developed by the Victorian Infectious Diseases Reference Laboratory (Australia), or other in-house or commercial assays already in use at their laboratories.
RESULTS
An in silico analysis of isolates showed a good match to assay primer/probes. The panel was distributed to 28 laboratories. Isolates were correctly identified in 98% of samples for detection and 99.6% for subtyping.
CONCLUSIONS
The WHO RSV EQA 2019-2020 showed that laboratories performed at high standards. Updating the composition of RSV molecular EQAs with contemporary strains to ensure representation of circulating strains, and ensuring primer matching with EQA panel viruses, is advantageous in assessing diagnostic competencies of laboratories. Ongoing EQAs are recommended because of continued evolution of mismatches between current circulating strains and existing primer sets.
Topics: United States; Humans; Respiratory Syncytial Virus, Human; Laboratories; Viruses; World Health Organization; Australia
PubMed: 36824313
DOI: 10.1111/irv.13073 -
Zhongguo Dang Dai Er Ke Za Zhi =... Jun 2023To investigate the distribution characteristics of non-bacterial pathogens in community-acquired pneumonia (CAP) in children.
OBJECTIVES
To investigate the distribution characteristics of non-bacterial pathogens in community-acquired pneumonia (CAP) in children.
METHODS
A total of 1 788 CAP children admitted to Shenyang Children's Hospital from December 2021 to November 2022 were selected. Multiple RT-PCR and capillary electrophoresis were used to detect 10 viral pathogens and 2 atypical pathogens, and serum antibodies of (Ch) and (MP) were detected. The distribution characteristics of different pathogens were analyzed.
RESULTS
Among the 1 788 CAP children, 1 295 children were pathogen-positive, with a positive rate of 72.43% (1 295/1 788), including a viral pathogen positive rate of 59.68% (1 067/1 788) and an atypical pathogen positive rate of 22.04% (394/1 788). The positive rates from high to low were MP, respiratory syncytial virus (RSV), influenza B virus (IVB), human metapneumovirus (HMPV), human rhinovirus (HRV), human parainfluenza virus (HPIV), influenza A virus (IVA), bocavirus (BoV), human adenovirus (HADV), Ch, and human coronavirus (HCOV). RSV and MP were the main pathogens in spring; MP had the highest positive rate in summer, followed by IVA; HMPV had the highest positive rate in autumn; IVB and RSV were the main pathogens in winter. The positive rate of MP in girls was higher than that in boys (<0.05), and there were no significant differences in other pathogens between genders (>0.05). The positivity rates of certain pathogens differed among age groups (<0.05): the positivity rate of MP was highest in the >6 year-old group; the positivity rates of RSV and Ch were highest in the <1 year-old group; the positivity rates of HPIV and IVB were highest in the 1 to <3 year-old group. RSV, MP, HRV, and HMPV were the main pathogens in children with severe pneumonia, while MP was the primary pathogen in children with lobar pneumonia, and MP, IVB, HMPV, RSV, and HRV were the top 5 pathogens in acute bronchopneumonia.
CONCLUSIONS
MP, RSV, IVB, HMPV, and HRV are the main pathogens of CAP in children, and there are certain differences in the positive rates of respiratory pathogens among children of different ages, genders, and seasons.
Topics: Humans; Child; Female; Male; Infant; Child, Preschool; Pneumonia; Respiratory Syncytial Virus, Human; Antibodies; Community-Acquired Infections; Hospitalization; Influenza B virus; Mycoplasma pneumoniae
PubMed: 37382134
DOI: 10.7499/j.issn.1008-8830.2212079 -
The Journal of Infectious Diseases Aug 2022
Topics: Humans; Infection Control; N95 Respirators; Respiratory Syncytial Virus Infections; Respiratory Syncytial Viruses; Viral Load
PubMed: 35535586
DOI: 10.1093/infdis/jiac197 -
Influenza and Other Respiratory Viruses Sep 2023Despite the growing recognition of a potentially significant respiratory syncytial virus (RSV) disease burden in adults, relevant evidence in the United Kingdom (UK) is... (Review)
Review
Despite the growing recognition of a potentially significant respiratory syncytial virus (RSV) disease burden in adults, relevant evidence in the United Kingdom (UK) is limited. This systematic literature review (SLR) aimed to identify the disease burden of RSV in UK adults, including certain high-risk subgroups and existing evidence gaps. Published studies (2011 onwards) reporting epidemiological, economic and clinical burden outcomes in UK adults (≥15 years) with RSV were identified from indexed databases, including MEDLINE, Embase and the Cochrane library. High-risk groups included elderly (≥65 years), immunocompromised, co-morbid and co-infected patients. Outcomes included RSV incidence/prevalence, mortality, clinical presentation and direct/indirect resource use/costs. Twenty-eight publications on 28 unique studies were identified, mostly in general/respiratory indicator ( = 17), elderly ( = 10) and immunocompromised ( = 6) cohorts. Main outcomes reported in the general/respiratory indicator cohort were RSV infection incidence (seasonal/annual: 0.09-17.9%/6.6-15.1%), mortality (8,482 deaths/season) and direct resource use (including mean general practitioner [GP] episodes/season: 487,247). Seasonal/annual incidence was 14.6-26.5%/0.7-16% in high-risk cohorts. Attributed to RSV in the elderly were 7,915 deaths/season and 175,070 mean GP episodes/season. Only two studies reported on co-morbid cohorts. Clinical burden outcomes were only reported in general and immunocompromised patients, and no evidence was found in any cohort on indirect economic burden or RSV complications. Evidence captured suggests that RSV may have a substantial burden in UK adults. However, available data were limited and highly heterogenous, with further studies needed to characterise the burden of RSV in adults and to validate our findings.
Topics: Aged; Humans; Adult; Respiratory Syncytial Virus, Human; Respiratory Syncytial Virus Infections; Cost of Illness; Databases, Factual; Evidence Gaps
PubMed: 37744994
DOI: 10.1111/irv.13188 -
Respirology (Carlton, Vic.) Nov 2021
Topics: Humans; Interleukin-17; Lung; Respiratory Syncytial Virus Infections; Respiratory Syncytial Viruses; Virus Diseases
PubMed: 34580948
DOI: 10.1111/resp.14158 -
The Lancet. Healthy Longevity Jun 2022Respiratory viral infections are typically more severe in older adults. Older adults are more vulnerable to infection and do not respond effectively to vaccines due to a...
Divergent age-related humoral correlates of protection against respiratory syncytial virus infection in older and young adults: a pilot, controlled, human infection challenge model.
BACKGROUND
Respiratory viral infections are typically more severe in older adults. Older adults are more vulnerable to infection and do not respond effectively to vaccines due to a combination of immunosenescence, so-called inflamm-ageing, and accumulation of comorbidities. Although age-related changes in immune responses have been described, the causes of this enhanced respiratory disease in older adults remain poorly understood. We therefore performed volunteer challenge with respiratory syncytial virus (RSV) in groups of younger and older adult volunteers. The aim of this study was to establish the safety and tolerability of this model and define age-related clinical, virological, and immunological outcomes.
METHODS
In this human infection challenge pilot study, adults aged 18-55 years and 60-75 years were assessed for enrolment using protocol-defined inclusion and exclusion criteria. Symptoms were documented by self-completed diaries and viral load determined by quantitative PCR of nasal lavage. Peripheral blood B cell frequencies were measured by enzyme-linked immunospot and antibodies against pre-fusion and post-fusion, NP, and G proteins in the blood and upper respiratory tract were measured. The study was registered with ClinicalTrials.gov, NCT03728413.
FINDINGS
381 adults aged 60-75 years (older cohort) and 19 adults aged 18-55 years (young cohort) were assessed for enrolment using protocol-defined inclusion and exclusion criteria between Nov 12, 2018, and Feb 26, 2020. 12 healthy volunteers aged 60-75 years and 21 aged 18-55 years were inoculated intranasally with RSV Memphis-37. Nine (67%) of the 12 older volunteers became infected, developing mild-to-moderate upper respiratory tract symptoms that resolved without serious adverse events or sequelae. Viral load peaked on day 6 post-inoculation and symptoms peaked between days 6 and 8. Increases in circulating IgG-positive and IgA-positive antigen-specific plasmablasts, serum neutralising antibodies, and pre-F specific IgG were similar younger and older adults. However, in contrast to young participants, secretory IgA titres in older volunteers failed to increase during infection and, unlike serum IgG, did not correlate with protection.
INTERPRETATION
Better understanding of age-related differences in clinical outcomes and immune correlates of protection can overcome reduction in vaccine efficacy with advancing age. We identify correlates of protection in older adults, revealing previously unrecognised factors which might have implications for targeted vaccine discovery and drug development in this vulnerable group.
FUNDING
Medical Research Council and GlaxoSmithKline EMINENT Consortium.
Topics: Aged; Antibodies, Viral; Humans; Immunoglobulin G; Pilot Projects; Respiratory Syncytial Virus Infections; Respiratory Syncytial Virus, Human; Young Adult
PubMed: 36098319
DOI: 10.1016/S2666-7568(22)00103-9 -
Frontiers in Cellular and Infection... 2022Respiratory syncytial virus (RSV) is a common cause of lower respiratory tract infections and responsible for a large proportion of mortality in children and the... (Review)
Review
Respiratory syncytial virus (RSV) is a common cause of lower respiratory tract infections and responsible for a large proportion of mortality in children and the elderly. There are no licensed vaccines available to date. Prophylaxis and therapeutic RSV-specific antibodies are limited to populations at high risk owing to high cost and uncertain clinical value. Receptors and host factors are two determinants important for virus entry and establishment of infection . The identification and understanding of viral receptors and host factors can help us to gain insight into the pathogenesis of RSV infection. Herein, we reviewed receptors and host factors that have been reported thus far. RSV could bind to CX3C chemokine receptor 1 and heparan sulfate proteoglycans the G protein, and to nucleolin, insulin-like growth factor-1 receptor, epidermal growth factor, and intercellular adhesion molecule-1 the F protein. Seven host restriction factors and 13 host factors essential for RSV infection were reviewed. We characterized the functions and their roles in the life cycle of RSV, trying to provide an update on the information of RSV-related receptors and host factors.
Topics: Antibodies, Viral; Epidermal Growth Factor; Humans; Respiratory Syncytial Virus Infections; Respiratory Syncytial Virus, Human
PubMed: 35281439
DOI: 10.3389/fcimb.2022.858629