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Influenza and Other Respiratory Viruses Jun 2024Respiratory syncytial virus (RSV) is increasingly recognized as a significant cause of lower respiratory tract disease (LRTD) in older adults. The Ad26.RSV.preF/RSV preF... (Randomized Controlled Trial)
Randomized Controlled Trial
A Randomized, Double-Blind, Placebo-Controlled, Phase 1 Study to Evaluate the Safety, Reactogenicity, and Immunogenicity of Single Vaccination of Ad26.RSV.preF-Based Regimen in Japanese Adults Aged 60 Years and Older.
BACKGROUND
Respiratory syncytial virus (RSV) is increasingly recognized as a significant cause of lower respiratory tract disease (LRTD) in older adults. The Ad26.RSV.preF/RSV preF protein vaccine demonstrated protective efficacy against RSV related LRTD in a Phase 2b study in the United States. Hence, Ad26.RSV.preF/RSV preF protein vaccine candidate was evaluated in the Japanese older adult population.
METHODS
This Phase 1 study evaluated safety, reactogenicity, and immunogenicity of Ad26.RSV.preF/RSV preF protein vaccine at dose level of 1 × 10 vp/150 μg in Japanese healthy adult aged ≥60 years. The study included a screening Phase, vaccination, 28-day follow up Phase, a 182-day follow-up period, and final visit on Day 183. A total of 36 participants were randomized in a 2:1 ratio to receive Ad26.RSV.preF/RSV preF protein vaccine (n = 24) or placebo (n = 12). After study intervention administration, the safety and immunogenicity analysis were performed as per planned schedule. Immune responses including virus-neutralizing and preF-specific binding antibodies were measured on Days 1, 15, 29, and 183.
RESULTS
There were no deaths, SAEs, or AEs leading to discontinuation reported during the study. The Ad26.RSV.preF/RSV preF protein vaccine had acceptable safety and tolerability profile with no safety concern in Japanese older adults. The Ad26.RSV.preF/RSV preF protein vaccine induced RSV-specific humoral immunity, with increase in antibody titers on Days 15 and 29 compared with baseline which was well maintained until Day 183.
CONCLUSIONS
A single dose of Ad26.RSV.preF/RSV preF protein vaccine had an acceptable safety and tolerability profile and induced RSV-specific humoral immunity in Japanese healthy adults.
TRIAL REGISTRATION
NCT number: NCT04354480; Clinical Registry number: CR108768.
Topics: Humans; Male; Aged; Female; Middle Aged; Double-Blind Method; Antibodies, Viral; Respiratory Syncytial Virus Infections; Respiratory Syncytial Virus Vaccines; Japan; Respiratory Syncytial Virus, Human; Vaccination; Immunogenicity, Vaccine; Aged, 80 and over; Adenoviridae; East Asian People
PubMed: 38880785
DOI: 10.1111/irv.13336 -
BMC Infectious Diseases Jun 2024Respiratory Syncytial Virus (RSV) is a leading cause of acute lower respiratory infection in children worldwide. Understanding its prevalence, variations, and...
INTRODUCTION
Respiratory Syncytial Virus (RSV) is a leading cause of acute lower respiratory infection in children worldwide. Understanding its prevalence, variations, and characteristics is vital, particularly in the context of the COVID-19 pandemic.
OBJECTIVE
The study aimed to investigate the RSV positivity rate, subtype prevalence, age and gender distribution, symptomatology, and co-infection rates during pre-pandemic and pandemic periods.
METHODS
We analyzed data from 15,381 patients tested for RSV between 2017 and 2023.
RESULTS
Our analysis revealed a 7.2% average RSV positivity rate in the pre-pandemic period, with significant fluctuations during the pandemic (1.5% in 2020 to 32.0% in 2021). We observed variations in RSVA and RSVB detection rates. The 0-4 years' age group was consistently the most affected, with a slight male predominance. Fever and cough were common symptoms. Therapeutic interventions, particularly antiviral usage and ventilation requirements, decreased during the pandemic. We also identified variations in co-infection rates with other respiratory viruses.
CONCLUSION
Our study offers critical insights into the impact of the COVID-19 pandemic on RSV prevalence, subtype distribution, patient characteristics, and clinical management. These findings underscore the need for ongoing surveillance and adaptive public health responses.
Topics: Humans; COVID-19; Respiratory Syncytial Virus Infections; India; Male; Female; Infant; Child, Preschool; Coinfection; Child; Prevalence; Respiratory Syncytial Virus, Human; Infant, Newborn; SARS-CoV-2; Adolescent; Adult; Middle Aged; Young Adult; Pandemics
PubMed: 38877428
DOI: 10.1186/s12879-024-09426-6 -
PloS One 2024Respiratory syncytial virus (RSV) is one of the major pathogens frequently associated with severe respiratory tract infections in younger children and older adults...
BACKGROUND
Respiratory syncytial virus (RSV) is one of the major pathogens frequently associated with severe respiratory tract infections in younger children and older adults globally. There is an unmet need with a lack of routine country-specific databases and/or RSV surveillance systems on RSV disease burden among adults in most low- and middle-income countries, including Cameroon. We aim to estimate the adult RSV burden needed to develop a framework for establishing an RSV surveillance database in Cameroon.
METHODS AND ANALYSIS
A two-phase study approach will be implemented, including a literature review and a review of medical records. First, a systematic review of available literature will provide insights into the current burden of RSV in adults in Cameroon, searching the following databases: Global Health, PubMed, CINAHL, Embase, African Journal Online Library, Scopus, Global Index Medicus, Cochrane databases, and grey literature search. Identified studies will be included if they reported on the RSV burden of disease among Cameroonian adults aged ≥18 years from 1st January 1990 to 31st December 2023. A narrative synthesis of the evidence will be provided. A meta-analysis will be conducted using a random effect model, when feasible. Two co-authors will independently perform data screening, extraction, and synthesis and will be reported according to the PRISMA-P guidelines for writing systematic review protocols. Secondly, a retrospective cohort design will permit data analysis on RSV among adults in the laboratory registers at the National Influenza Center. Medical records will be reviewed to link patients' files from emanating hospitals to capture relevant demographic, laboratory, and clinical data. The International Classification of Diseases and Clinical Modifications 10th revision (ICD-10-CM) codes will be used to classify the different RSV outcomes retrospectively.
RESULTS
The primary outcome is quantifying the RSV burden among the adult population, which can help inform policy on establishing an RSV surveillance database in Cameroon. The secondary outcomes include (i) estimates of RSV prevalence among Cameroonian adult age groups, (ii) RSV determinants, and (iii) clinical outcomes, including proportions of RSV-associated morbidity and/or death among age-stratified Cameroonian adults with medically attended acute respiratory tract infections.
CONCLUSIONS
The evidence generated from the two projects will be used for further engagement with relevant stakeholders, including policymakers, clinicians, and researchers, to develop a framework for systematically establishing an RSV surveillance database in Cameroon. This study proposal has been registered (CRD42023460616) with the University of York Center for Reviews and Dissemination of the International Prospective Register of Systematic Reviews (PROSPERO).
Topics: Humans; Cameroon; Respiratory Syncytial Virus Infections; Respiratory Syncytial Virus, Human; Adult; Systematic Reviews as Topic
PubMed: 38861519
DOI: 10.1371/journal.pone.0303468 -
Human Vaccines & Immunotherapeutics Dec 2024Respiratory syncytial virus (RSV) is the leading cause of lower respiratory tract infections in young children and associated with most bronchiolitis- and...
Respiratory syncytial virus (RSV) is the leading cause of lower respiratory tract infections in young children and associated with most bronchiolitis- and pneumonia-related hospitalizations. A new preventive monoclonal antibody (MAb), nirsevimab, has been launched in the United States, Luxembourg, and France, and was recently approved to be given in a population-based manner throughout Spain. This study aimed to have a first pre-immunization insight into the Spanish parental knowledge about bronchiolitis, RSV, and nirsevimab immunization. Parents in Murcia with children <2 years of age up to the date of September 1, 2023, were selected to complete a questionnaire. The primary endpoint was the parental knowledge about bronchiolitis, RSV, and nirsevimab. A total of 3,217 responses were analyzed. The majority (95.8%) were aware of bronchiolitis. Meanwhile, 46.6% of the respondents knew about RSV, most of them only after the first child's birth. Information about RSV or bronchiolitis was mainly obtained from family members, with only 4.8% reporting having been informed by Health care Professionals (HCPs). Only 11.2% of respondents were aware of nirsevimab. Nonetheless, these were not entirely satisfied with the information received (score of 3.3 out of 5) and shared that HCPs should be the primary source of information. The present survey then highlights the need for better and more efficient educational strategies directed to all parents/legal guardians. It also sheds some light on the different factors that should be considered to improve awareness of RSV immunization to decrease its burden in Spain and beyond.
Topics: Humans; Spain; Respiratory Syncytial Virus Infections; Parents; Female; Male; Health Knowledge, Attitudes, Practice; Infant; Surveys and Questionnaires; Adult; Immunization Programs; Respiratory Syncytial Virus, Human; Bronchiolitis; Antibodies, Monoclonal, Humanized; Middle Aged; Young Adult; Infant, Newborn
PubMed: 38857859
DOI: 10.1080/21645515.2024.2357439 -
Signal Transduction and Targeted Therapy Jun 2024Respiratory syncytial virus (RSV) is the major cause of bronchiolitis and pneumonia in young children and the elderly. There are currently no approved RSV-specific...
Respiratory syncytial virus (RSV) is the major cause of bronchiolitis and pneumonia in young children and the elderly. There are currently no approved RSV-specific therapeutic small molecules available. Using high-throughput antiviral screening, we identified an oral drug, the prenylation inhibitor lonafarnib, which showed potent inhibition of the RSV fusion process. Lonafarnib exhibited antiviral activity against both the RSV A and B genotypes and showed low cytotoxicity in HEp-2 and human primary bronchial epithelial cells (HBEC). Time-of-addition and pseudovirus assays demonstrated that lonafarnib inhibits RSV entry, but has farnesyltransferase-independent antiviral efficacy. Cryo-electron microscopy revealed that lonafarnib binds to a triple-symmetric pocket within the central cavity of the RSV F metastable pre-fusion conformation. Mutants at the RSV F sites interacting with lonafarnib showed resistance to lonafarnib but remained fully sensitive to the neutralizing monoclonal antibody palivizumab. Furthermore, lonafarnib dose-dependently reduced the replication of RSV in BALB/c mice. Collectively, lonafarnib could be a potential fusion inhibitor for RSV infection.
Topics: Humans; Respiratory Syncytial Virus Infections; Pyridines; Mice; Animals; Respiratory Syncytial Virus, Human; Viral Fusion Proteins; Farnesyltranstransferase; Antiviral Agents; Piperidines; Mice, Inbred BALB C; Protein Conformation; Dibenzocycloheptenes
PubMed: 38853183
DOI: 10.1038/s41392-024-01858-5 -
Human Vaccines & Immunotherapeutics Dec 2024A maternal vaccine and long-acting monoclonal antibody (mAb) were recently approved to protect infants against respiratory syncytial virus (RSV). We identified subgroups...
A maternal vaccine and long-acting monoclonal antibody (mAb) were recently approved to protect infants against respiratory syncytial virus (RSV). We identified subgroups of pregnant people with different preferences for RSV preventives and respondent characteristics associated with subgroup membership. An online survey, including a discrete choice experiment (DCE), was conducted among US pregnant people. RSV preventive attributes included effectiveness, duration of protection during RSV season, injection recipient/timing, preventive type (vaccine or mAb), and type of visit required to receive injection. In DCE choice tasks, pregnant people selected between two hypothetical preventive profiles with varying attribute-levels and a no-preventive option. Logistic regression, including latent class analysis (LCA), was used to analyze the data. Of 992 pregnant people (mean age: 30.0 years), 60.3% were expecting their second/later birth. LCA identified three preference subgroups: 'Effectiveness' (preventive choice mostly driven by increases in effectiveness; 51.4% class membership probability), 'Season' (preventive choice mostly driven by improvement in duration of protection during the RSV season; 39.2% class membership probability), and 'No Preventive' (frequently chose no-preventive option; 9.4% class membership probability). 'Effectiveness' and 'Season' preferred maternal vaccine over mAb; mAb was preferred by 'No Preventive.' Perceiving RSV as serious for infants, higher health literacy, and lower household income were associated with 'Effectiveness.' Perceiving RSV as serious for pregnant people was associated with 'Season.' Perceiving RSV to not be serious for pregnant people and not being employed were associated with 'No Preventive.' Subgroups of pregnant people vary in preferences for RSV preventives. Most pregnant people preferred a maternal vaccine, although some may be more willing to accept alternative preventive options.
Topics: Humans; Female; Pregnancy; Respiratory Syncytial Virus Infections; United States; Adult; Respiratory Syncytial Virus Vaccines; Latent Class Analysis; Young Adult; Respiratory Syncytial Virus, Human; Infant; Surveys and Questionnaires; Patient Preference; Vaccination; Pregnant Women; Antibodies, Monoclonal; Adolescent
PubMed: 38847198
DOI: 10.1080/21645515.2024.2358566 -
Influenza and Other Respiratory Viruses Jun 2024In September 2023, France was one of the first countries that started a national immunisation campaign with nirsevimab, a new monoclonal antibody against respiratory...
Nirsevimab Effectiveness Against Cases of Respiratory Syncytial Virus Bronchiolitis Hospitalised in Paediatric Intensive Care Units in France, September 2023-January 2024.
In September 2023, France was one of the first countries that started a national immunisation campaign with nirsevimab, a new monoclonal antibody against respiratory syncytial virus (RSV). Using data from a network of paediatric intensive care units (PICUs), we aimed to estimate nirsevimab effectiveness against severe cases of RSV bronchiolitis in France. We conducted a case-control study based on the test-negative design and included 288 infants reported by 20 PICUs. We estimated nirsevimab effectiveness at 75.9% (48.5-88.7) in the main analysis and 80.6% (61.6-90.3) and 80.4% (61.7-89.9) in two sensitivity analyses. These real-world estimates confirmed the efficacy observed in clinical studies.
Topics: Humans; France; Respiratory Syncytial Virus Infections; Infant; Intensive Care Units, Pediatric; Case-Control Studies; Male; Female; Hospitalization; Respiratory Syncytial Virus, Human; Antibodies, Monoclonal, Humanized; Antiviral Agents; Bronchiolitis; Bronchiolitis, Viral; Treatment Outcome
PubMed: 38840301
DOI: 10.1111/irv.13311 -
Respiratory Research Jun 2024The concurrent circulation of SARS-CoV-2 with other respiratory viruses is unstoppable and represents a new diagnostic reality for clinicians and clinical microbiology...
BACKGROUND
The concurrent circulation of SARS-CoV-2 with other respiratory viruses is unstoppable and represents a new diagnostic reality for clinicians and clinical microbiology laboratories. Multiplexed molecular testing on automated platforms that focus on the simultaneous detection of multiple respiratory viruses in a single tube is a useful approach for current and future diagnosis of respiratory infections in the clinical setting.
METHODS
Two time periods were included in the study: from February to April 2022, an early 2022 period, during the gradual lifting of COVID-19 prevention measures in the country, and from October 2022 to April 2023, the 2022/23 respiratory infections season. We analysed a total of 1,918 samples in the first period and 18,131 respiratory samples in the second period using a multiplex molecular assay for the simultaneous detection of Influenza A (Flu-A), Influenza B (Flu-B), Human Respiratory Syncytial Virus (HRSV) and SARS-CoV-2.
RESULTS
The results from early 2022 showed a strong dominance of SARS-CoV-2 infections with 1,267/1,918 (66.1%) cases. Flu-A was detected in 30/1,918 (1.6%) samples, HRSV in 14/1,918 (0.7%) samples, and Flu-B in 2/1,918 (0.1%) samples. Flu-A/SARS-CoV-2 co-detections were observed in 11/1,267 (0.9%) samples, and HRSV/SARS-CoV-2 co-detection in 5/1,267 (0.4%) samples. During the 2022/23 winter respiratory season, SARS-CoV-2 was detected in 1,738/18,131 (9.6%), Flu-A in 628/18,131 (3.5%), Flu-B in 106/18,131 (0.6%), and HRSV in 505/18,131 (2.8%) samples. Interestingly, co-detections were present to a similar extent as in early 2022.
CONCLUSION
The results show that the multiplex molecular approach is a valuable tool for the simultaneous laboratory diagnosis of SARS-CoV-2, Flu-A/B, and HRSV in hospitalized and outpatients. Infections with Flu-A/B, and HRSV occurred shortly after the COVID-19 control measures were lifted, so a strong reoccurrence of various respiratory infections and co-detections in the post COVID-19 period was to be expected.
Topics: Humans; COVID-19; Influenza B virus; Influenza, Human; SARS-CoV-2; Respiratory Syncytial Virus Infections; Respiratory Syncytial Virus, Human; Influenza A virus; Male; Female; Coinfection; Middle Aged; Adult; Molecular Diagnostic Techniques; Seasons; Aged
PubMed: 38840154
DOI: 10.1186/s12931-024-02862-7 -
Mikrochimica Acta Jun 2024A trendsetting direct competitive-based biosensing tool has been developed and implemented for the determination of the polyunsaturated fatty acid arachidonic acid...
A trendsetting direct competitive-based biosensing tool has been developed and implemented for the determination of the polyunsaturated fatty acid arachidonic acid (ARA), a highly significant biological regulator with decisive roles in viral infections. The designed methodology involves a competitive reaction between the target endogenous ARA and a biotin-ARA competitor for the recognition sites of anti-ARA antibodies covalently attached to the surface of carboxylic acid-coated magnetic microbeads (HOOC-MµBs), followed by the enzymatic label of the biotin-ARA residues with streptavidin-horseradish peroxidase (Strep-HRP) conjugate. The resulting bioconjugates were magnetically trapped onto the sensing surface of disposable screen-printed carbon transducers (SPCEs) to monitor the extent of the biorecognition reaction through amperometry. The operational functioning of the exhaustively optimized and characterized immunosensing bioplatform was highly convenient for the quantitative determination of ARA in serum samples from severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2-) and respiratory syncytial virus (RSV)-infected individuals in a rapid, affordable, trustful, and sensitive manner.
Topics: Humans; Arachidonic Acid; COVID-19; Biosensing Techniques; SARS-CoV-2; Horseradish Peroxidase; Respiratory Syncytial Viruses; Immunoassay; Streptavidin; Biotin; Limit of Detection
PubMed: 38834823
DOI: 10.1007/s00604-024-06440-y -
Frontiers in Immunology 2024Activated lung ILC2s produce large quantities of IL-5 and IL-13 that contribute to eosinophilic inflammation and mucus production following respiratory syncytial virus...
Activated lung ILC2s produce large quantities of IL-5 and IL-13 that contribute to eosinophilic inflammation and mucus production following respiratory syncytial virus infection (RSV). The current understanding of ILC2 activation during RSV infection, is that ILC2s are activated by alarmins, including IL-33, released from airway epithelial cells in response to viral-mediated damage. Thus, high levels of RSV neutralizing maternal antibody generated from maternal immunization would be expected to reduce IL-33 production and mitigate ILC2 activation. Here we report that lung ILC2s from mice born to RSV-immunized dams become activated despite undetectable RSV replication. We also report, for the first time, expression of activating and inhibitory Fcgamma receptors on ILC2s that are differentially expressed in offspring born to immunized versus unimmunized dams. Alternatively, ex vivo IL-33-mediated activation of ILC2s was mitigated following the addition of antibody: antigen immune complexes. Further studies are needed to confirm the role of Fcgamma receptor ligation by immune complexes as an alternative mechanism of ILC2 regulation in RSV-associated eosinophilic lung inflammation.
Topics: Animals; Respiratory Syncytial Virus Infections; Mice; Female; Mice, Inbred BALB C; Lung; Interleukin-33; Respiratory Syncytial Viruses; Lymphocytes; Immunization; Receptors, IgG; Antibodies, Viral; Pregnancy; Respiratory Syncytial Virus Vaccines
PubMed: 38827738
DOI: 10.3389/fimmu.2024.1374818