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European Journal of Pharmaceutical... Dec 2023Chronic respiratory diseases and infections are among the largest contributors to death globally, many of which still have no cure, including chronic obstructive... (Review)
Review
Chronic respiratory diseases and infections are among the largest contributors to death globally, many of which still have no cure, including chronic obstructive pulmonary disorder, idiopathic pulmonary fibrosis, and respiratory syncytial virus among others. Pulmonary therapeutics afford untapped potential for treating lung infection and disease through direct delivery to the site of action. However, the ability to innovate new therapeutic paradigms for respiratory diseases will rely on modeling the human lung microenvironment and including key cellular interactions that drive disease. One key feature of the lung microenvironment is the air-liquid interface (ALI). ALI interface modeling techniques, using cell-culture inserts, organoids, microfluidics, and precision lung slices (PCLS), are rapidly developing; however, one major component of these models is lacking-innate immune cell populations. Macrophages, neutrophils, and dendritic cells, among others, represent key lung cell populations, acting as the first responders during lung infection or injury. Innate immune cells respond to and modulate stromal cells and bridge the gap between the innate and adaptive immune system, controlling the bodies response to foreign pathogens and debris. In this article, we review the current state of ALI culture systems with a focus on innate immune cells and suggest ways to build on current models to add complexity and relevant immune cell populations.
Topics: Humans; Lung; Pulmonary Disease, Chronic Obstructive; Macrophages; Respiratory Syncytial Virus, Human; Immunity; Immunity, Innate
PubMed: 37770004
DOI: 10.1016/j.ejps.2023.106596 -
Frontiers in Cellular and Infection... 2020Respiratory Syncytial Virus (RSV) is a highly prevalent virus that affects the majority of the population. The virus can cause severe disease in vulnerable populations... (Review)
Review
Respiratory Syncytial Virus (RSV) is a highly prevalent virus that affects the majority of the population. The virus can cause severe disease in vulnerable populations leading to high hospitalization rates from bronchiolitis or secondary bacterial infections leading to pneumonia. Two early and non-structural proteins (Ns1 and Ns2), strongly over-ride the antiviral innate system but also diminish the adaptive response as well. This review will cover interactions of Ns1 and Ns2 with the host antiviral response with a focus on alterations to signaling pathways, cytokine gene expression, and effects of the Ns proteins on mitochondria.
Topics: Cytokines; Gene Expression; Humans; Respiratory Syncytial Virus Infections; Respiratory Syncytial Virus, Human; Signal Transduction; Viral Nonstructural Proteins
PubMed: 32509597
DOI: 10.3389/fcimb.2020.00225 -
Nature Communications Aug 2021Human respiratory syncytial virus (RSV) is a major cause of lower respiratory tract infection in young children globally, but little is known about within-host RSV... (Clinical Trial)
Clinical Trial
Human respiratory syncytial virus (RSV) is a major cause of lower respiratory tract infection in young children globally, but little is known about within-host RSV diversity. Here, we characterised within-host RSV populations using deep-sequencing data from 319 nasopharyngeal swabs collected during 2017-2020. RSV-B had lower consensus diversity than RSV-A at the population level, while exhibiting greater within-host diversity. Two RSV-B consensus sequences had an amino acid alteration (K68N) in the fusion (F) protein, which has been associated with reduced susceptibility to nirsevimab (MEDI8897), a novel RSV monoclonal antibody under development. In addition, several minor variants were identified in the antigenic sites of the F protein, one of which may confer resistance to palivizumab, the only licensed RSV monoclonal antibody. The differences in within-host virus populations emphasise the importance of monitoring for vaccine efficacy and may help to explain the different prevalences of monoclonal antibody-escape mutants between the two subgroups.
Topics: Aged; Antigenic Variation; Female; Genetic Variation; Humans; Infant; Male; Mutation, Missense; Respiratory Syncytial Virus Infections; Respiratory Syncytial Virus, Human; Viral Proteins; Virus Replication
PubMed: 34446722
DOI: 10.1038/s41467-021-25265-4 -
Pneumologie (Stuttgart, Germany) Jun 2020RSV induces an acute viral disease with involvement of the respiratory tract. It can be notably life-threatening for infants but also for older adults. New RSV-subtypes... (Review)
Review
RSV induces an acute viral disease with involvement of the respiratory tract. It can be notably life-threatening for infants but also for older adults. New RSV-subtypes are constantly evolving globally. The knowledge about epidemiology, hygiene measures, diagnostics and clinical feature is essential not only for the paediatrician. Vaccines or specific therapeutics are still missing. This article gives an overview with focus on RSV in adults. In addition, molecular pathological characteristics of the virus are explained, research approaches concerning vaccines and therapeutics are mentioned and current problems in management are discussed.
Topics: Humans; Respiratory Insufficiency; Respiratory Syncytial Virus Infections; Respiratory Syncytial Virus, Human
PubMed: 32557509
DOI: 10.1055/a-0853-2881 -
Frontiers in Public Health 2022The COVID-19 pandemic impacts different health aspects. Concomitant with the adoption of non-pharmaceutical interventions (NPIs) to reduce the spread of SARS-CoV-2,...
BACKGROUND
The COVID-19 pandemic impacts different health aspects. Concomitant with the adoption of non-pharmaceutical interventions (NPIs) to reduce the spread of SARS-CoV-2, global surveillance studies reported a reduction in occurrence of respiratory pathogens like influenza A and B virus (IAV & IBV) and respiratory syncytial virus (RSV). We hypothesized to observe this collateral benefit on viral respiratory infection epidemiology in young children.
METHODS
Respiratory samples of children aged below 6 years, presenting at the outpatient clinic, emergency department, or pediatric infectious diseases department of the University Hospitals Leuven, between April 2017 and April 2021 were retrospectively analyzed. The occurrence (positivity rate), and seasonal patterns of viral respiratory infections were described. Chi-squared or Fisher's exact test (and Bonferroni correction) were used to explore differences in occurrence between 2020-2021 and previous 12-month (April to April) periods.
RESULTS
We included 3020 samples (453 respiratory panels, 2567 single SARS-CoV-2 PCR tests). IAV and IBV were not detected from March and January 2020, respectively. For IAV, positivity rate in 2020-2021 (0%, = 0) was significantly different from 2018-2019 (12.4%, = 17) ( < 0.001) and 2019-2020 (15.4%, = 19) ( < 0.001). IBV positivity rate in 2020-2021 (0%, = 0) was not significantly different from previous periods. RSV occurrence was significantly lower in 2020-2021 (3.2%, = 3), compared to 2017-2018 (15.0%, = 15) ( = 0.006), 2018-2019 (16.1%, = 22) ( = 0.002) and 2019-2020 (22.8%, = 28) ( < 0.001). The RSV (winter) peak was absent and presented later (March-April 2021). Positivity rate of parainfluenza virus 3 (PIV-3) was significantly higher in 2020-2021 (11.8%, = 11) than 2017-2018 (1%, = 1) ( = 0.002). PIV-3 was absent from April 2020 to January 2021, whereas no clear seasonal pattern was distinguished the other years. For the other viruses tested, no significant differences in occurrence were observed between 2020-2021 and previous periods. From March 2020 onwards, 20 cases (0.7%) of SARS-CoV-2 were identified.
CONCLUSION
These findings reinforce the hypothesis of NPIs impacting the epidemiology of influenza viruses and RSV in young children. Compared to previous periods, no IAV and IBV cases were observed in the 2020-2021 study period, and the RSV peak occurred later. Since the pandemic is still ongoing, continuation of epidemiological surveillance, even on a larger scale, is indicated.
Topics: COVID-19; Child; Child, Preschool; Humans; Pandemics; Respiratory Syncytial Viruses; Retrospective Studies; SARS-CoV-2
PubMed: 36203684
DOI: 10.3389/fpubh.2022.931242 -
The Journal of Infectious Diseases Oct 2023Respiratory syncytial virus (RSV) causes significant disease burden in older adults. MVA-BN-RSV is a novel poxvirus-vectored vaccine encoding internal and external RSV... (Randomized Controlled Trial)
Randomized Controlled Trial
BACKGROUND
Respiratory syncytial virus (RSV) causes significant disease burden in older adults. MVA-BN-RSV is a novel poxvirus-vectored vaccine encoding internal and external RSV proteins.
METHODS
In a phase 2a randomized double-blind, placebo-controlled trial, healthy participants aged 18 to 50 years received MVA-BN-RSV or placebo, then were challenged 4 weeks later with RSV-A Memphis 37b. Viral load was assessed from nasal washes. RSV symptoms were collected. Antibody titers and cellular markers were assessed before and after vaccination and challenge.
RESULTS
After receiving MVA-BN-RSV or placebo, 31 and 32 participants, respectively, were challenged. Viral load areas under the curve from nasal washes were lower (P = .017) for MVA-BN-RSV (median = 0.00) than placebo (median = 49.05). Total symptom scores also were lower (median = 2.50 and 27.00, respectively; P = .004). Vaccine efficacy against symptomatic, laboratory-confirmed or culture-confirmed infection was 79.3% to 88.5% (P = .022 and .013). Serum immunoglobulin A and G titers increased approximately 4-fold after MVA-BN-RSV vaccination. Interferon-γ-producing cells increased 4- to 6-fold after MVA-BN-RSV in response to stimulation with the encoded RSV internal antigens. Injection site pain occurred more frequently with MVA-BN-RSV. No serious adverse events were attributed to vaccination.
CONCLUSIONS
MVA-BN-RSV vaccination resulted in lower viral load and symptom scores, fewer confirmed infections, and induced humoral and cellular responses.
CLINICAL TRIALS REGISTRATION
NCT04752644.
Topics: Aged; Humans; Antibodies, Viral; Antigens, Viral; Respiratory Syncytial Virus Infections; Respiratory Syncytial Virus Vaccines; Respiratory Syncytial Virus, Human; Smallpox Vaccine; Vaccinia virus
PubMed: 37079393
DOI: 10.1093/infdis/jiad108 -
Viruses May 2022Many countries have implemented public health and social measures (PHSMs) to control the spread of severe acute respiratory syndrome coronavirus-2 (SARS-CoV-2). Although... (Review)
Review
Many countries have implemented public health and social measures (PHSMs) to control the spread of severe acute respiratory syndrome coronavirus-2 (SARS-CoV-2). Although the PHSMs are targeted at SARS-CoV-2 transmission control, they directly or indirectly impact the epidemiology of different respiratory viral diseases. The purpose of this study was to investigate the collateral impact of PHSMs used during the coronavirus disease 2019 (COVID-19) pandemic on the epidemiology of other respiratory viruses, including influenza, parainfluenza, respiratory syncytial virus, rhinovirus, and adenovirus infections. We conducted a systematic review of the published literature on changes in the incidence of respiratory viral diseases and detection rates of the respiratory viruses during COVID-19 pandemic, lasting from 2020-2021, published between December 2019 and March 2022 in , and databases. We identified an overall decrease of 23-94% in the incidence of respiratory viral diseases and a decrease of 0-98% in the detection of the viruses. Our study suggests that the PHSMs implemented during COVID-19 pandemic reduced the incidence of respiratory viral diseases and transmission of respiratory viruses. At the time of this study, and as governments relax PHSMs, public health authorities should prepare for a probable increase in the burden of respiratory viral diseases.
Topics: COVID-19; Humans; Pandemics; Public Health; Respiratory Syncytial Virus, Human; Respiratory Tract Infections; SARS-CoV-2; Viruses
PubMed: 35632810
DOI: 10.3390/v14051071 -
Frontiers in Immunology 2023Respiratory syncytial virus (RSV) can cause lower respiratory tract disease in infants and elderly populations. Despite decades of research, there remains no safe and...
INTRODUCTION
Respiratory syncytial virus (RSV) can cause lower respiratory tract disease in infants and elderly populations. Despite decades of research, there remains no safe and approved RSV vaccine. Previously, we showed that an RSV G glycoprotein subunit vaccine candidate with a single point mutation within the central conserved domain (CCD), i.e. S177Q, considerably improved immunogenicity.
METHODS
Here, we examine the development of nanoparticle (NP) vaccines having either an RSV G protein CCD with wild-type sequence (NPWT) or an S177Q mutation (NP-S177Q). The NP vaccine immunogens were adjuvanted with monophosphoryl lipid A (MPLA), a TLR4 agonist to improve Th1- type responses. BALB/c mice were primed with 10 μg of NP-WT vaccine, NPS177Q, or vehicle, rested, and then boosted with a high (25 μg) or low (10 μg) dose of the NP-WT or NP-S177Q homologous candidate and subsequently challenged with RSV A2.
RESULTS
The results showed that mice boosted with NP-S177Q developed superior immunogenicity and neutralizing antibodies compared to NP-WT boosting. IgG from either NP-S177Q or NP-WT vaccinated mice did not interfere with fractalkine (CX3CL1) binding to CX3CR1 and effectively blocked G protein CX3C-CX3CR1 binding. Both NP-WT and NP-S177Q vaccination induced similar neutralizing antibodies to RSV in challenged mice compared to vehicle control. NP-S177Q boosting improved correlates of protection including reduced BAL cell infiltration following RSV challenge. However, the NP vaccine platform will require improvement due to the poor solubility and the unexpectedly weaker Th1-type IgG2a response.
DISCUSSION
The results from this study support further NP-S177Q vaccine candidate development.
Topics: Mice; Animals; Respiratory Syncytial Virus Infections; Respiratory Syncytial Virus Vaccines; Antibodies, Viral; Respiratory Syncytial Virus, Human; Antibodies, Neutralizing; GTP-Binding Proteins
PubMed: 37457705
DOI: 10.3389/fimmu.2023.1215323 -
The Lancet. Digital Health Nov 2023
Topics: Humans; Infant; Respiratory Syncytial Virus, Human; Respiratory Syncytial Virus Infections
PubMed: 37890899
DOI: 10.1016/S2589-7500(23)00206-6 -
Virology Journal Oct 2023Respiratory syncytial virus (RSV), a member of the Pneumoviridae family, can cause severe acute lower respiratory tract infection in infants, young children,... (Review)
Review
Respiratory syncytial virus (RSV), a member of the Pneumoviridae family, can cause severe acute lower respiratory tract infection in infants, young children, immunocompromised individuals and elderly people. RSV is associated with an augmented innate immune response, enhanced secretion of inflammatory cytokines, and necrosis of infected cells. Oxidative stress, which is mainly characterized as an imbalance in the production of reactive oxygen species (ROS) and antioxidant responses, interacts with all the pathophysiologic processes above and is receiving increasing attention in RSV infection. A gradual accumulation of evidence indicates that ROS overproduction plays an important role in the pathogenesis of severe RSV infection and serves as a major factor in pulmonary inflammation and tissue damage. Thus, antioxidants seem to be an effective treatment for severe RSV infection. This article mainly reviews the information on oxidative stress and ROS-mediated cellular events during RSV infection for the first time.
Topics: Child; Infant; Humans; Aged; Child, Preschool; Antioxidants; Reactive Oxygen Species; Respiratory Syncytial Virus Infections; Oxidative Stress; Respiratory Syncytial Virus, Human
PubMed: 37798799
DOI: 10.1186/s12985-023-02194-w