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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 -
Jornal de Pediatria 2023To identify and assess the current evidence available about the costs of managing hospitalized pediatric patients diagnosed with Respiratory Syncytial Virus (RSV) and... (Review)
Review
OBJECTIVE
To identify and assess the current evidence available about the costs of managing hospitalized pediatric patients diagnosed with Respiratory Syncytial Virus (RSV) and Parainfluenza Virus Type 3 (PIV3) in upper-middle-income countries.
METHODS
The authors conducted a systematic review across seven key databases from database inception to July 2022. Costs extracted were converted into 2022 International Dollars using the Purchasing Power Parity-adjusted. PROSPERO identifier: CRD42020225757.
RESULTS
No eligible study for PIV3 was recovered. For RSV, cost analysis and COI studies were performed for populations in Colombia, China, Malaysia, and Mexico. Comparing the total economic impact, the lowest cost per patient at the pediatric ward was observed in Malaysia ($ 347.60), while the highest was in Colombia ($ 709.66). On the other hand, at pediatric ICU, the lowest cost was observed in China ($ 1068.26), while the highest was in Mexico ($ 3815.56). Although there is no consensus on the major cost driver, all included studies described that the medications (treatment) consumed over 30% of the total cost. A high rate of inappropriate prescription drugs was observed.
CONCLUSION
The present study highlighted how RSV infection represents a substantial economic burden to health care systems and to society. The findings of the included studies suggest a possible association between baseline risk status and expenditures. Moreover, it was observed that an important amount of the cost is destinated to treatments that have no evidence or support in most clinical practice guidelines.
Topics: Humans; Child; Infant; Developing Countries; Financial Stress; Respiratory Syncytial Virus Infections; Respiratory Syncytial Virus, Human; Parainfluenza Virus 3, Human; Hospitalization
PubMed: 37247828
DOI: 10.1016/j.jped.2023.05.003 -
Vaccine Apr 2024Chinese Hamster Ovary (CHO) cells, employed primarily for manufacturing monoclonal antibodies and other recombinant protein (r-protein) therapeutics, are emerging as a... (Review)
Review
Chinese Hamster Ovary (CHO) cells, employed primarily for manufacturing monoclonal antibodies and other recombinant protein (r-protein) therapeutics, are emerging as a promising host for vaccine antigen production. This is exemplified by the recently approved CHO cell-derived subunit vaccines (SUV) against respiratory syncytial virus (RSV) and varicella-zoster virus (VZV), as well as the enveloped virus-like particle (eVLP) vaccine against hepatitis B virus (HBV). Here, we summarize the design, production, and immunogenicity features of these vaccine and review the most recent progress of other CHO-derived vaccines in pre-clinical and clinical development. We also discuss the challenges associated with vaccine production in CHO cells, with a focus on ensuring viral clearance for eVLP products.
Topics: Cricetinae; Animals; Humans; CHO Cells; Cricetulus; Respiratory Syncytial Virus Infections; Antibodies, Neutralizing; Antibodies, Viral; Respiratory Syncytial Virus, Human; Vaccines, Virus-Like Particle; Herpesvirus 3, Human; Vaccines, Subunit; Respiratory Syncytial Virus Vaccines
PubMed: 38503664
DOI: 10.1016/j.vaccine.2024.03.034 -
Respiratory syncytial virus knowledge, attitudes, and perceptions among adults in the United States.Human Vaccines & Immunotherapeutics Dec 2024Respiratory syncytial virus (RSV) is associated with considerable morbidity and mortality among older adults (aged ≥60 years) and adults with certain chronic...
Respiratory syncytial virus (RSV) is associated with considerable morbidity and mortality among older adults (aged ≥60 years) and adults with certain chronic conditions in the United States (US). Despite this burden, no previous studies have assessed the knowledge, attitudes, and perceptions (KAP) of RSV among these populations. This study evaluates RSV-related KAP among US adults at increased risk of severe RSV infection. A cross-sectional, web-based survey was administered from May to June 2022 to better understand respiratory infection- and RSV-related KAP among US adults who are at risk of severe RSV infection. The survey included ≥200 adults in each of 4 subgroups: adults aged 60-89 years, and adults aged 18-59 years with ≥1 chronic cardiovascular condition, chronic pulmonary condition, or diabetes mellitus. Survey responses were analyzed descriptively overall and by subgroup, with exploratory logistic regression modeling used to evaluate characteristics associated with RSV awareness and concern. Among the 827 survey respondents, only 43.3% had ever heard of RSV ( = 358/827). The study identified key knowledge gaps (e.g. bacterial vs. viral nature of respiratory infections, RSV seasonality, common RSV symptoms, extent to which RSV causes respiratory infections in specific patient populations). Although 33.7% of RSV-aware adults ( = 120/356) reported being worried/very worried about RSV, 67.3% ( = 241/358) rarely consider RSV as a potential cause of their cold/flu-like symptoms. Results from this study highlight important knowledge gaps related to RSV, perceived risk, and severity of RSV. Findings can be used to support the development of tailored education efforts to support RSV prevention.
Topics: Humans; United States; Aged; Respiratory Syncytial Virus Infections; Health Knowledge, Attitudes, Practice; Cross-Sectional Studies; Respiratory Syncytial Virus, Human; Respiratory Tract Infections; Chronic Disease; Hospitalization
PubMed: 38297921
DOI: 10.1080/21645515.2024.2303796 -
Influenza and Other Respiratory Viruses Nov 2023A viral infection can modify the risk to subsequent viral infections via cross-protective immunity, increased immunopathology, or disease-driven behavioral change. There...
BACKGROUND
A viral infection can modify the risk to subsequent viral infections via cross-protective immunity, increased immunopathology, or disease-driven behavioral change. There is limited understanding of virus-virus interactions due to lack of long-term population-level data.
METHODS
Our study leverages passive surveillance data of 10 human acute respiratory viruses from Beijing, Chongqing, Guangzhou, and Shanghai collected during 2009 to 2019: influenza A and B viruses; respiratory syncytial virus A and B; human parainfluenza virus (HPIV), adenovirus, metapneumovirus (HMPV), coronavirus, bocavirus (HBoV), and rhinovirus (HRV). We used a multivariate Bayesian hierarchical model to evaluate correlations in monthly prevalence of test-positive samples between virus pairs, adjusting for potential confounders.
RESULTS
Of 101,643 lab-tested patients, 33,650 tested positive for any acute respiratory virus, and 4,113 were co-infected with multiple viruses. After adjusting for intrinsic seasonality, long-term trends and multiple comparisons, Bayesian multivariate modeling found positive correlations for HPIV/HRV in all cities and for HBoV/HRV and HBoV/HMPV in three cities. Models restricted to children further revealed statistically significant associations for another ten pairs in three of the four cities. In contrast, no consistent correlation across cities was found among adults. Most virus-virus interactions exhibited substantial spatial heterogeneity.
CONCLUSIONS
There was strong evidence for interactions among common respiratory viruses in highly populated urban settings. Consistent positive interactions across multiple cities were observed in viruses known to typically infect children. Future intervention programs such as development of combination vaccines may consider spatially consistent virus-virus interactions for more effective control.
Topics: Child; Adult; Humans; Infant; Beijing; Respiratory Tract Infections; Bayes Theorem; China; Viruses; Virus Diseases; Respiratory Syncytial Virus, Human
PubMed: 37964991
DOI: 10.1111/irv.13212 -
Current Opinion in Pediatrics Jun 2024Human respiratory syncytial virus (RSV) causes acute respiratory infection in individuals of all age groups. It is the most common pathogen identified in infants and... (Review)
Review
PURPOSE OF REVIEW
Human respiratory syncytial virus (RSV) causes acute respiratory infection in individuals of all age groups. It is the most common pathogen identified in infants and young children with acute lower respiratory infection. Although most infants and young children experience mild, cold-like symptoms, some infants develop severe lower respiratory tract disease such as pneumonia and bronchiolitis that may result in an emergency department visit or hospitalization.
RECENT FINDINGS
In the United States, hospitalization rates have risen during the last decades, and while premature infants with chronic lung disease and congenital heart disease are at increased risk for severe presentations, the majority of hospitalizations occur in previously healthy infants. Until recently, RSV prophylaxis was only available for former preterm infants and those with certain underlying medical conditions.
SUMMARY
The need for preventive interventions against RSV is crucial. This paper will provide a review of the vaccine development, the spectrum of RSV prophylaxis, current challenges associated with the cost, insurance coverage and equitable distribution of targeted therapies.
Topics: Child, Preschool; Humans; Infant; Infant, Newborn; Antiviral Agents; Hospitalization; Respiratory Syncytial Virus Infections; Respiratory Syncytial Virus Vaccines; Respiratory Syncytial Virus, Human; United States; Vaccine Development
PubMed: 38351889
DOI: 10.1097/MOP.0000000000001339 -
BMC Pulmonary Medicine Sep 2023Respiratory syncytial virus (RSV) infection in adults remains less recognized and understood, both socially and clinically, compared to influenza virus infection. This...
BACKGROUND
Respiratory syncytial virus (RSV) infection in adults remains less recognized and understood, both socially and clinically, compared to influenza virus infection. This retrospective study aims to delineate and compare the clinical manifestations of adult RSV and influenza virus infections in the lower respiratory tract, thereby enhancing awareness of RSV lower respiratory tract infection and providing strategic insights for its prevention and treatment.
METHODS
Clinical data from January 2019 to December 2020 were analyzed for 74 patients with RSV and 129 patients with influenza A/B virus lower respiratory tract infections who were admitted to respiratory or intensive care units. All patients had complete clinical data with positive IgM and negative IgG viral antibodies. Comparison parameters included onset timing, baseline data, clinical manifestations, supplementary examination results, treatment methods, and prognosis, while logistic regression was employed to ascertain the correlation of clinical features between the two patient groups.
RESULTS
In comparison to the influenza group, the RSV group presented less frequently with fever at admission but exhibited a higher incidence of dyspnea and wheezing on pulmonary auscultation (P < 0.01). RSV infection was more prevalent among patients with underlying diseases, particularly chronic obstructive pulmonary disease (COPD) and demonstrated a higher probability of co-infections, most notably with Mycoplasma (P < 0.01). The RSV group had significantly higher lymphocyte counts (P < 0.01) and exhibited more incidences of pleural thickening, pulmonary fibrosis, and emphysema (P < 0.05). The use of non-invasive mechanical ventilation was more common, and hospital stays were longer in the RSV group compared to the influenza group (P < 0.05). Logistic multivariate regression analysis further revealed that age and tachypnea incidence were significantly higher in the RSV group (P < 0.05).
CONCLUSION
Compared to influenza virus infection, adults with COPD are more susceptible to RSV infection. Moreover, RSV infection elevates the risk of co-infection with Mycoplasma and may lead to conditions such as pleural thickening, pulmonary fibrosis, and emphysema. The requirement for non-invasive mechanical ventilation is higher in RSV-infected patients, who also tend to have longer hospital stays. Therefore, greater awareness and preventive strategies against RSV infection are imperative.
Topics: Adult; Humans; Respiratory Syncytial Viruses; Retrospective Studies; Influenza, Human; Pulmonary Fibrosis; Respiratory Tract Infections; Pulmonary Disease, Chronic Obstructive; Pulmonary Emphysema; Coinfection; Emphysema; Orthomyxoviridae
PubMed: 37715219
DOI: 10.1186/s12890-023-02648-5 -
Frontiers in Immunology 2023The immune mechanisms supporting partial protection from reinfection and disease by the respiratory syncytial virus (RSV) have not been fully characterized. In older...
INTRODUCTION
The immune mechanisms supporting partial protection from reinfection and disease by the respiratory syncytial virus (RSV) have not been fully characterized. In older adults, symptoms are typically mild but can be serious in patients with comorbidities when the infection extends to the lower respiratory tract.
METHODS
This study formed part of the RESCEU older-adults prospective-cohort study in Northern Europe (2017-2019; NCT03621930) in which a thousand participants were followed over an RSV season. Peripheral-blood samples (taken pre-season, post-season, during illness and convalescence) were analyzed from participants who (i) had a symptomatic acute respiratory tract infection by RSV (RSV-ARTI; N=35) or (ii) asymptomatic RSV infection (RSV-Asymptomatic; N=16). These analyses included evaluations of antibody (Fc-mediated-) functional features and cell-mediated immunity, in which univariate and machine-learning (ML) models were used to explore differences between groups.
RESULTS
Pre-RSV-season peripheral-blood biomarkers were predictive of symptomatic RSV infection. T-cell data were more predictive than functional antibody data (area under receiver operating characteristic curve [AUROC] for the models were 99% and 76%, respectively). The pre-RSV season T-cell phenotypes which were selected by the ML modelling and which were more frequent in RSV-Asymptomatic group than in the RSV-ARTI group, coincided with prominent phenotypes identified during convalescence from RSV-ARTI (e.g., IFN-γ+, TNF-α+ and CD40L+ for CD4+, and IFN-γ+ and 4-1BB+ for CD8+).
CONCLUSION
The evaluation and statistical modelling of numerous immunological parameters over the RSV season suggests a primary role of cellular immunity in preventing symptomatic RSV infections in older adults.
Topics: Humans; Aged; Respiratory Syncytial Virus Infections; T-Lymphocytes; Cohort Studies; Prospective Studies; Convalescence; Respiratory Syncytial Virus, Human; Antibodies, Viral
PubMed: 37936699
DOI: 10.3389/fimmu.2023.1260146 -
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 -
Frontiers in Immunology 2023The primary goal of this work is to broaden and enhance the options for induction of protective CD8 T cells against HIV-1 and respiratory pathogens.
Combined intranasal and intramuscular parainfluenza 5-, simian adenovirus ChAdOx1- and poxvirus MVA-vectored vaccines induce synergistically HIV-1-specific T cells in the mucosa.
INTRODUCTION
The primary goal of this work is to broaden and enhance the options for induction of protective CD8 T cells against HIV-1 and respiratory pathogens.
METHODS
We explored the advantages of the parainfluenza virus 5 (PIV5) vector for delivery of pathogen-derived transgenes alone and in combination with the in-human potent regimen of simian adenovirus ChAdOx1 prime-poxvirus MVA boost delivering bi-valent mosaic of HIV-1 conserved regions designated HIVconsvX.
RESULTS
We showed in BALB/c mice that the PIV5 vector expressing the HIVconsvX immunogens could be readily incorporated with the other two vaccine modalities into a single regimen and that for specific vector combinations, mucosal CD8 T-cell induction was enhanced synergistically by a combination of the intranasal and intramuscular routes of administration.
DISCUSSION
Encouraging safety and immunogenicity data from phase 1 human trials of ChAdOx1- and MVA-vectored vaccines for HIV-1, and PIV5-vectored vaccines for SARS-CoV-2 and respiratory syncytial virus pave the way for combining these vectors for HIV-1 and other indications in humans.
Topics: Mice; Animals; Humans; Adenoviruses, Simian; HIV-1; CD8-Positive T-Lymphocytes; COVID-19 Vaccines; COVID-19; SARS-CoV-2; Respiratory Syncytial Virus, Human
PubMed: 37529048
DOI: 10.3389/fimmu.2023.1186478