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The Journal of Infectious Diseases Apr 2022Protection against human respiratory syncytial virus (RSV) remains an unmet need potentially addressable by maternal immunization. This phase 1/2 study evaluated a... (Randomized Controlled Trial)
Randomized Controlled Trial
BACKGROUND
Protection against human respiratory syncytial virus (RSV) remains an unmet need potentially addressable by maternal immunization. This phase 1/2 study evaluated a bivalent prefusion F vaccine (RSVpreF) with antigens from RSV subgroups A and B.
METHODS
Adults 18-49 years old (N = 618) were randomized to receive placebo or 60, 120, or 240 µg RSVpreF with or without Al(OH)3. Safety and immunogenicity were evaluated.
RESULTS
RSVpreF recipients more frequently reported local reactions and systemic events than placebo recipients; these were mostly mild or moderate. No vaccine-related serious adverse events occurred through 12 months postvaccination. All RSVpreF formulations induced 1-month postvaccination virus-neutralizing titers higher than those associated with protection of high-risk infants by palivizumab, the only prophylactic currently available for RSV. Geometric mean fold rises (GMFRs) across RSVpreF doses/formulations were 10.6-16.9 for RSV A and 10.3-19.8 for RSV B at 1 month postvaccination, greater than those historically elicited by postfusion F vaccines. GMFRs were 3.9-5.2 and 3.7-5.1, respectively, at 12 months postvaccination.
CONCLUSIONS
RSVpreF formulations were safe, well tolerated, and induced robust neutralizing responses in adults. These findings support development of RSVpreF, which is being evaluated in a pivotal phase 3 study for maternal immunization.
CLINICAL TRIALS REGISTRATION
NCT03529773.
Topics: Adolescent; Adult; Antibodies, Neutralizing; Antibodies, Viral; Humans; Middle Aged; Respiratory Syncytial Virus Infections; Respiratory Syncytial Virus Vaccines; Respiratory Syncytial Virus, Human; Viral Fusion Proteins; Young Adult
PubMed: 34932102
DOI: 10.1093/infdis/jiab612 -
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 -
Nature Medicine May 2023Nirsevimab is an extended half-life monoclonal antibody specific for the prefusion conformation of the respiratory syncytial virus (RSV) F protein, which has been...
Nirsevimab is an extended half-life monoclonal antibody specific for the prefusion conformation of the respiratory syncytial virus (RSV) F protein, which has been studied in preterm and full-term infants in the phase 2b and phase 3 MELODY trials. We analyzed serum samples collected from 2,143 infants during these studies to characterize baseline levels of RSV-specific immunoglobulin G antibodies and neutralizing antibodies (NAbs), duration of RSV NAb levels following nirsevimab administration, the risk of RSV exposure during the first year of life and the infant's adaptive immune response to RSV following nirsevimab administration. Baseline RSV antibody levels varied widely; consistent with reports that maternal antibodies are transferred late in the third trimester, preterm infants had lower baseline RSV antibody levels than full-term infants. Nirsevimab recipients had RSV NAb levels >140-fold higher than baseline at day 31 and remained >50-fold higher at day 151 and >7-fold higher at day 361. Similar seroresponse rates to the postfusion form of RSV F protein in nirsevimab recipients (68-69%) compared with placebo recipients (63-70%; not statistically significant) suggest that while nirsevimab protects from RSV disease, it still allows an active immune response. In summary, nirsevimab provided sustained, high levels of NAb throughout an infant's first RSV season and prevented RSV disease while allowing the development of an immune response to RSV.
Topics: Humans; Infant; Infant, Newborn; Infant, Premature; Respiratory Syncytial Virus Infections; Antibodies, Viral; Respiratory Syncytial Virus, Human; Antibodies, Neutralizing; Immunity
PubMed: 37095249
DOI: 10.1038/s41591-023-02316-5 -
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 -
Human Vaccines & Immunotherapeutics May 2021Respiratory Syncytial Virus (RSV) causes lower respiratory tract infections that can be severe and sometimes fatal. The risk for severe RSV infection is highest in... (Randomized Controlled Trial)
Randomized Controlled Trial
A phase 1, randomized, placebo-controlled study to evaluate the safety and immunogenicity of an mRNA-based RSV prefusion F protein vaccine in healthy younger and older adults.
Respiratory Syncytial Virus (RSV) causes lower respiratory tract infections that can be severe and sometimes fatal. The risk for severe RSV infection is highest in infants and older adults. A safe and effective RSV vaccine for older adults represents a serious unmet medical need due to higher morbidity and mortality in this age group. In this randomized, partially double-blind, placebo-controlled, phase 1 dose-escalation study, we evaluated the safety, tolerability and immunogenicity of an investigational messenger ribonucleic acid (mRNA) vaccine encoding the RSV fusion protein (F) stabilized in the prefusion conformation. The study was conducted in healthy younger adults (ages ≥18 and ≤49 years) and healthy older adults (ages ≥60 and ≤79 years). Participants received mRNA-1777 (V171) or placebo as a single intramuscular dose. For each dose level, three sentinel participants were administered open-label mRNA-1777 (V171). Seventy-two younger adults were randomized and administered 25, 100, or 200 µg mRNA-1777 (V171) or placebo, and 107 older adults were randomized and administered 25, 100, 200 or 300 µg mRNA-1777 (V171) or placebo. Primary objectives were safety and tolerability and secondary objectives included humoral and cell-mediated immunogenicity. All dose levels of mRNA-1777 (V171) were generally well tolerated and no serious adverse events related to the vaccine were reported. Immunization with mRNA-1777 (V171) elicited a humoral immune response as measured by increases in RSV neutralizing antibody titers, serum antibody titers to RSV prefusion F protein, D25 competing antibody titers to RSV prefusion F protein, and cell-mediated immune responses to RSV-F peptides.
Topics: Aged; Antibodies, Neutralizing; Antibodies, Viral; Humans; Immunogenicity, Vaccine; Middle Aged; RNA, Messenger; Respiratory Syncytial Virus Infections; Respiratory Syncytial Virus Vaccines; Respiratory Syncytial Virus, Human; Viral Fusion Proteins
PubMed: 33121346
DOI: 10.1080/21645515.2020.1829899 -
Journal of Virology Apr 2022Respiratory syncytial virus (RSV) is a leading cause of pediatric acute respiratory infection worldwide. There are currently no approved vaccines or antivirals to combat...
Respiratory syncytial virus (RSV) is a leading cause of pediatric acute respiratory infection worldwide. There are currently no approved vaccines or antivirals to combat RSV disease. A few transformed cell lines and two historic strains have been extensively used to study RSV. Here, we reported a thorough molecular and cell biological characterization of HEp-2 and A549 cells infected with one of four strains of RSV representing both major subgroups as well as historic and more contemporary genotypes (RSV/A/Tracy [GA1], RSV/A/Ontario [ON], RSV/B/18537 [GB1], and RSV/B/Buenos Aires [BA]) via measurements of viral replication kinetics and viral gene expression, immunofluorescence-based imaging of gross cellular morphology and cell-associated RSV, and measurements of host response, including transcriptional changes and levels of secreted cytokines and growth factors. Infection with the respiratory syncytial virus (RSV) early in life is essentially guaranteed and can lead to severe disease. Most RSV studies have involved either of two historic RSV/A strains infecting one of two cell lines, HEp-2 or A549 cells. However, RSV contains ample variation within two evolving subgroups (A and B), and HEp-2 and A549 cell lines are genetically distinct. Here, we measured viral action and host response in both HEp-2 and A549 cells infected with four RSV strains from both subgroups and representing both historic and more contemporary strains. We discovered a subgroup-dependent difference in viral gene expression and found A549 cells were more potently antiviral and more sensitive, albeit subtly, to viral variation. Our findings revealed important differences between RSV subgroups and two widely used cell lines and provided baseline data for experiments with model systems better representative of natural RSV infection.
Topics: A549 Cells; Antiviral Agents; Cell Line; Host Microbial Interactions; Humans; Respiratory Syncytial Virus Infections; Respiratory Syncytial Virus, Human; Severity of Illness Index; Species Specificity; Virus Replication
PubMed: 35285685
DOI: 10.1128/jvi.01904-21 -
Clinical Infectious Diseases : An... Jul 2022Respiratory syncytial virus (RSV), parainfluenza virus (PIV), and human metapneumovirus (hMPV) are increasingly associated with chronic lung allograft dysfunction (CLAD)... (Meta-Analysis)
Meta-Analysis
Respiratory Syncytial Virus, Human Metapneumovirus, and Parainfluenza Virus Infections in Lung Transplant Recipients: A Systematic Review of Outcomes and Treatment Strategies.
BACKGROUND
Respiratory syncytial virus (RSV), parainfluenza virus (PIV), and human metapneumovirus (hMPV) are increasingly associated with chronic lung allograft dysfunction (CLAD) in lung transplant recipients (LTR). This systematic review primarily aimed to assess outcomes of RSV/PIV/hMPV infections in LTR and secondarily to assess evidence regarding the efficacy of ribavirin.
METHODS
Relevant databases were queried and study outcomes extracted using a standardized method and summarized.
RESULTS
Nineteen retrospective and 12 prospective studies were included (total 1060 cases). Pooled 30-day mortality was low (0-3%), but CLAD progression 180-360 days postinfection was substantial (pooled incidences 19-24%) and probably associated with severe infection. Ribavirin trended toward effectiveness for CLAD prevention in exploratory meta-analysis (odds ratio [OR] 0.61, [0.27-1.18]), although results were highly variable between studies.
CONCLUSIONS
RSV/PIV/hMPV infection was followed by a high CLAD incidence. Treatment options, including ribavirin, are limited. There is an urgent need for high-quality studies to provide better treatment options for these infections.
Topics: Humans; Lung; Metapneumovirus; Parainfluenza Virus 1, Human; Parainfluenza Virus 2, Human; Paramyxoviridae Infections; Prospective Studies; Respiratory Syncytial Virus Infections; Respiratory Syncytial Virus, Human; Respiratory Tract Infections; Retrospective Studies; Ribavirin; Transplant Recipients
PubMed: 35022697
DOI: 10.1093/cid/ciab969 -
The Journal of Infectious Diseases Nov 2023No overall estimate of respiratory syncytial virus (RSV)-associated hospitalizations in children aged under 5 years has been published for the European Union (EU). We...
BACKGROUND
No overall estimate of respiratory syncytial virus (RSV)-associated hospitalizations in children aged under 5 years has been published for the European Union (EU). We aimed to estimate the RSV hospitalization burden in children aged under 5 years in EU countries and Norway, by age group.
METHODS
We collated national RSV-associated hospitalization estimates calculated using linear regression models via the RESCEU project for Denmark, England, Finland, Norway, the Netherlands, and Scotland, 2006-2018. Additional estimates were obtained from a systematic review. Using multiple imputation and nearest neighbor matching methods, we estimated overall RSV-associated hospitalizations and rates in the EU.
RESULTS
Additional estimates for 2 countries (France and Spain) were found in the literature. In the EU, an average of 245 244 (95% confidence interval [CI], 224 688-265 799) yearly hospital admissions with a respiratory infection per year were associated with RSV in children aged under 5 years, with most cases occurring among children aged under 1 year (75%). Infants aged under 2 months represented the most affected group (71.6 per 1000 children; 95% CI, 66.6-76.6).
CONCLUSIONS
Our findings will help support decisions regarding prevention efforts and represent an important benchmark to understand changes in the RSV burden following the introduction of RSV immunization programs in Europe.
Topics: Child; Child, Preschool; Humans; Infant; European Union; Hospitalization; Respiratory Syncytial Virus Infections; Respiratory Syncytial Virus, Human; Respiratory Tract Infections; Systematic Reviews as Topic
PubMed: 37246724
DOI: 10.1093/infdis/jiad188 -
The Journal of Infectious Diseases Nov 2023Respiratory syncytial virus (RSV) is a major cause of lower respiratory tract infections in adults that can result in hospitalizations. Estimating RSV-associated...
BACKGROUND
Respiratory syncytial virus (RSV) is a major cause of lower respiratory tract infections in adults that can result in hospitalizations. Estimating RSV-associated hospitalization is critical for planning RSV-related healthcare across Europe.
METHODS
We gathered RSV-associated hospitalization estimates from the RSV Consortium in Europe (RESCEU) for adults in Denmark, England, Finland, Norway, Netherlands, and Scotland from 2006 to 2017. We extrapolated these estimates to 28 European Union (EU) countries using nearest-neighbor matching, multiple imputations, and 2 sets of 10 indicators.
RESULTS
On average, 158 229 (95% confidence interval [CI], 140 865-175 592) RSV-associated hospitalizations occur annually among adults in the EU (≥18 years); 92% of these hospitalizations occur in adults ≥65 years. Among 75-84 years, the annual average is estimated at 74 519 (95% CI, 69 923-79 115) at a rate of 2.24 (95% CI, 2.10-2.38) per 1000. Among ≥85 years, the annual average is estimated at 37 904 (95% CI, 32 444-43 363) at a rate of 2.99 (95% CI, 2.56-3.42).
CONCLUSIONS
Our estimates of RSV-associated hospitalizations in adults are the first analysis integrating available data to provide the disease burden across the EU. Importantly, for a condition considered in the past to be primarily a disease of young children, the average annual hospitalization estimate in adults was lower but of a similar magnitude to the estimate in young children (0-4 years): 158 229 (95% CI, 140 865-175 592) versus 245 244 (95% CI, 224 688-265 799).
Topics: Child; Humans; Adult; Infant; Child, Preschool; Respiratory Syncytial Virus Infections; European Union; Respiratory Syncytial Virus, Human; Respiratory Tract Infections; Hospitalization
PubMed: 37246742
DOI: 10.1093/infdis/jiad189