New Interventions to Prevent Respiratory Syncytial Virus Disease in Infants-Time for Equitable Global Access.
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ABSTRACT:
SUBMITTER: Cunningham S
PROVIDER: S-EPMC10273123 | biostudies-literature | 2023 Jun
REPOSITORIES: biostudies-literature
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New Interventions to Prevent Respiratory Syncytial Virus Disease in Infants-Time for Equitable Global Access.
Cunningham Steve S Zar Heather J HJ
American journal of respiratory and critical care medicine 20230601 12
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Project description:The lung is a critical prophylaxis target for clinically important infectious agents, including human respiratory syncytial virus (RSV) and influenza. Here, we develop a modular, synthetic mRNA-based approach to express neutralizing antibodies directly in the lung via aerosol, to prevent RSV infections. First, we express palivizumab, which reduces RSV F copies by 90.8%. Second, we express engineered, membrane-anchored palivizumab, which prevents detectable infection in transfected cells, reducing in vitro titer and in vivo RSV F copies by 99.7% and 89.6%, respectively. Finally, we express an anchored or secreted high-affinity, anti-RSV F, camelid antibody (RSV aVHH and sVHH). We demonstrate that RSV aVHH, but not RSV sVHH, significantly inhibits RSV 7 days post transfection, and we show that RSV aVHH is present in the lung for at least 28 days. Overall, our data suggests that expressing membrane-anchored broadly neutralizing antibodies in the lungs could potentially be a promising pulmonary prophylaxis approach.
| S-EPMC6167369 | biostudies-literature
Project description:BackgroundRespiratory syncytial virus (RSV) is a common cause of acute respiratory infection in children. One of the most important strategies for treatment of an RSV infection is to decide whether the patient needs respiratory support. This study aimed to assess the validity and clinical benefit of the Global Respiratory Severity Score (GRSS) and the Wang bronchiolitis severity score (WBSS) for clinical decision-making regarding providing respiratory support (high-flow nasal cannula, nasal continuous positive airway pressure, or ventilator) in infants with an RSV infection.Study design and methodsThis retrospective cohort study enrolled 250 infants aged under 10 months who were admitted to Atsugi City Hospital with an RSV infection between January 2012 and December 2019. The utility of these scores was evaluated for assessing the need for respiratory support through decision curve analysis by calculating the optimal GRSS and WBSS cut-offs for predicting the need for respiratory support.ResultsTwenty-six infants (10.4%) received respiratory support. The optimal cut-offs for the GRSS and the WBSS were 4.52 and 7, respectively. Decision curve analysis suggested that the GRSS was a better predictive tool than the WBSS if the probability of needing respiratory support was 10-40%.ConclusionsThe GRSS was clinically useful in determining the need for respiratory support in infants aged under 10 months with an RSV infection.
| S-EPMC8248615 | biostudies-literature
Project description:ObjectivesRespiratory syncytial virus (RSV) pneumonia is a leading cause of infant mortality worldwide. The risk of RSV infection associated with preterm birth is not well-characterized in resource-limited settings. We aimed to obtain precise estimates of risk factors and disease burden of RSV in infants in rural southern Nepal.MethodsPregnant women were enrolled, and along with their infants, followed to six months after birth with active weekly home-based surveillance for acute respiratory illness (ARI). Mid-nasal swabs were obtained and tested for RSV by PCR for all illness episodes. Birth outcomes were assessed at a postpartum home visit.Results311 (9%) of 3509 infants had an RSV ARI. RSV ARI incidence decreased from 551/1000 person-years in infants born between 28 and 31 weeks to 195/1000 person-years in infants born full-term (p = 0.017). Of 220 infants (71%) evaluated in the health system, 41 (19%) visited a hospital or physician. Of 287 infants with an assessment performed, 203 (71%) had a lower respiratory tract infection.ConclusionsIn a rural south Asian setting with intensive home-based surveillance, RSV caused a significant burden of respiratory illness. Preterm infants had the highest incidence of RSV ARI, and should be considered a priority group for RSV preventive interventions in resource-limited settings.
| S-EPMC4942356 | biostudies-literature
Project description:BackgroundRespiratory syncytial virus (RSV) is a leading cause of pediatric death, with >99% of mortality occurring in low- and lower middle-income countries. At least half of RSV-related deaths are estimated to occur in the community, but clinical characteristics of this group of children remain poorly characterized.MethodsThe RSV Global Online Mortality Database (RSV GOLD), a global registry of under-5 children who have died with RSV-related illness, describes clinical characteristics of children dying of RSV through global data sharing. RSV GOLD acts as a collaborative platform for global deaths, including community mortality studies described in this supplement. We aimed to compare the age distribution of infant deaths <6 months occurring in the community with in-hospital.ResultsWe studied 829 RSV-related deaths <1 year of age from 38 developing countries, including 166 community deaths from 12 countries. There were 629 deaths that occurred <6 months, of which 156 (25%) occurred in the community. Among infants who died before 6 months of age, median age at death in the community (1.5 months; IQR: 0.8-3.3) was lower than in-hospital (2.4 months; IQR: 1.5-4.0; P < .0001). The proportion of neonatal deaths was higher in the community (29%, 46/156) than in-hospital (12%, 57/473, P < 0.0001).ConclusionsWe observed that children in the community die at a younger age. We expect that maternal vaccination or immunoprophylaxis against RSV will have a larger impact on RSV-related mortality in the community than in-hospital. This case series of RSV-related community deaths, made possible through global data sharing, allowed us to assess the potential impact of future RSV vaccines.
| S-EPMC8411255 | biostudies-literature
Project description:This SuperSeries is composed of the SubSeries listed below.
2024-05-29 | GSE232687 | GEO
Project description:Purpose of reviewWith interventions to prevent respiratory syncytial virus (RSV) infection within reach, this review aims to provide healthcare professionals with the latest information necessary to inform parents and assess the potential impact of RSV prevention on everyday practice. We address frequently asked questions for parental counseling.Recent findingsNumerous studies emphasize the major burden of RSV on young children, parents, healthcare and society. In the first year of life, about 14% of healthy term infants visit a doctor and 2% require hospitalization due to RSV. In older children (1--5 years), RSV infections and associated morbidity (wheeze, acute otitis media) are major drivers of outpatient visits. A novel maternal RSV vaccine and long-acting mAb can provide protection during infants' first months of life. This maternal vaccine showed 70.9% efficacy against severe RSV infection within 150 days after birth; the mAb nirsevimab reduces medically attended RSV infections by 79.5% within 150 days after administration. Both gained regulatory approval in the USA (FDA) and Europe (EMA).SummaryNovel RSV immunizations hold promise to reduce the RSV burden in infants, with substantial impact on everyday practice. Tailored parental guidance will be instrumental for successful implementation. Awaiting pediatric vaccines, RSV infections beyond infancy will still pose a significant outpatient burden.
| S-EPMC10919273 | biostudies-literature
Project description:BackgroundRespiratory syncytial virus (RSV) is the dominant cause of severe lower respiratory tract infection in infants, with the most severe cases concentrated among younger infants.MethodsHealthy pregnant women, at 28 weeks 0 days through 36 weeks 0 days of gestation, with an expected delivery date near the start of the RSV season, were randomly assigned in an overall ratio of approximately 2:1 to receive a single intramuscular dose of RSV fusion (F) protein nanoparticle vaccine or placebo. Infants were followed for 180 days to assess outcomes related to lower respiratory tract infection and for 364 days to assess safety. The primary end point was RSV-associated, medically significant lower respiratory tract infection up to 90 days of life, and the primary analysis of vaccine efficacy against the primary end point was performed in the per-protocol population of infants (prespecified criterion for success, lower bound of the 97.52% confidence interval [CI] of ≥30%).ResultsA total of 4636 women underwent randomization, and there were 4579 live births. During the first 90 days of life, the percentage of infants with RSV-associated, medically significant lower respiratory tract infection was 1.5% in the vaccine group and 2.4% in the placebo group (vaccine efficacy, 39.4%; 97.52% CI, -1.0 to 63.7; 95% CI, 5.3 to 61.2). The corresponding percentages for RSV-associated lower respiratory tract infection with severe hypoxemia were 0.5% and 1.0% (vaccine efficacy, 48.3%; 95% CI, -8.2 to 75.3), and the percentages for hospitalization for RSV-associated lower respiratory tract infection were 2.1% and 3.7% (vaccine efficacy, 44.4%; 95% CI, 19.6 to 61.5). Local injection-site reactions among the women were more common with vaccine than with placebo (40.7% vs. 9.9%), but the percentages of participants who had other adverse events were similar in the two groups.ConclusionsRSV F protein nanoparticle vaccination in pregnant women did not meet the prespecified success criterion for efficacy against RSV-associated, medically significant lower respiratory tract infection in infants up to 90 days of life. The suggestion of a possible benefit with respect to other end-point events involving RSV-associated respiratory disease in infants warrants further study. (Funded by Novavax and the Bill and Melinda Gates Foundation; ClinicalTrials.gov NCT02624947.).
| S-EPMC7299433 | biostudies-literature
Project description:BackgroundEarly-life severe respiratory syncytial virus (RSV) bronchiolitis is a risk factor for childhood asthma. Because azithromycin may attenuate airway inflammation during RSV bronchiolitis, we evaluated whether it would reduce the occurrence of post-RSV recurrent wheeze.MethodsWe prospectively enrolled 200 otherwise healthy 1- to 18-month-old children hospitalized with RSV bronchiolitis in this single-center, double-blind, placebo-controlled study and randomly assigned them to receive oral azithromycin (10 mg/kg daily for 7 days, followed by 5 mg/kg daily for 7 days) or placebo. Randomization was stratified by recent open-label antibiotic use. The primary outcome was the occurrence of recurrent wheeze, defined as a third episode of post-RSV wheeze over the following 2 to 4 years.ResultsAs an indication of the biologic activity of azithromycin, nasal wash interleukin-8 levels, at day 14 after randomization, were lower among azithromycin-treated participants (P<0.01). Despite evidence of biologic activity, azithromycin did not reduce the risk of post-RSV recurrent wheeze (47% in the azithromycin group vs. 36% in the placebo group; adjusted hazard ratio, 1.45; 95% confidence interval [CI], 0.92 to 2.29; P=0.11). Azithromycin also did not modify the risk of recurrent wheeze among participants already receiving other antibiotic treatment at the time of enrollment (hazard ratio, 0.94; 95% CI, 0.43 to 2.07). There was a potential signal among antibiotic-naïve participants who received azithromycin to have an increased risk of recurrent wheeze (hazard ratio, 1.79; 95% CI, 1.03 to 3.1).ConclusionsAzithromycin therapy for 14 days during acute severe RSV bronchiolitis did not reduce recurrent wheeze occurrence over the following 2 to 4 years. Our data suggest no benefit of azithromycin administration with the goal of preventing recurrent wheeze in later life. (Funded by the National Heart, Lung, and Blood Institute; ClinicalTrials.gov number, NCT02911935.).
| S-EPMC10448891 | biostudies-literature
Project description:In this study we investigated whether there exists a genomic signature that can accurately predict the course of a respiratory syncytial virus (RSV) infection in hospitalized young infants. We used early blood microarray transcriptome profiles from 39 infants that were followed until recovery and of which the level of disease severity was determined retrospectively. Applying support vector machine learning on age by sex standardized transcriptomic data, an 84 gene signature was identified that discriminated hospitalized infants with eventually less severe RSV infection from infants that suffered from most severe RSV disease.
2016-11-11 | E-MTAB-5195 | biostudies-arrayexpress
Project description:Respiratory syncytial virus Genome sequencing
| PRJNA1050228 | ENA