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Pediatric Annals Mar 2024
Topics: Humans; Immunization; Vaccination; Respiratory Syncytial Virus, Human
PubMed: 38466331
DOI: 10.3928/19382359-20240214-01 -
Science Translational Medicine Jun 2022Respiratory syncytial virus (RSV) is a substantial cause of morbidity and mortality globally. A candidate RSV prefusion (pre-F)-stabilized subunit vaccine, DS-Cav1, has...
Respiratory syncytial virus (RSV) is a substantial cause of morbidity and mortality globally. A candidate RSV prefusion (pre-F)-stabilized subunit vaccine, DS-Cav1, has previously been shown to elicit potent and durable neutralizing activity in a phase 1 clinical trial in healthy adults. Here, we used fluorescently labeled probes and flow cytometry to evaluate the antigen specificity and phenotype of RSV F-specific B cells longitudinally after DS-Cav1 immunization. Peripheral blood mononuclear cells (PBMCs) collected at time points before the first immunization through the end of the trial at 44 weeks were assessed by flow cytometry. Our data demonstrate a rapid increase in the frequency of pre-F-specific IgG and IgA B cells after the first immunization and a modest increase after a second immunization at week 12. Nearly all F-specific B cells down-regulated CD21 and up-regulated the proliferation marker CD71 after the first immunization, with less pronounced activation after the second immunization. Memory B cells (CD27CD21) specific for pre-F remained elevated above baseline at 44 weeks after vaccination. DS-Cav1 vaccination also activated human metapneumovirus (HMPV) cross-reactive B cells capable of binding prefusion-stabilized HMPV F protein and increased HMPV F-binding antibodies and neutralizing activity for HMPV in some participants. In summary, vaccination with RSV pre-F resulted in the expansion and activation of RSV and HMPV F-specific B cells that were maintained above baseline for at least 10 months and could contribute to long-term pneumovirus immunity.
Topics: Antibodies, Neutralizing; Antibodies, Viral; Humans; Leukocytes, Mononuclear; Pneumovirus; Respiratory Syncytial Virus Infections; Respiratory Syncytial Virus Vaccines; Respiratory Syncytial Virus, Human; Viral Fusion Proteins
PubMed: 35731888
DOI: 10.1126/scitranslmed.abo5032 -
Shock (Augusta, Ga.) Jan 2017Immunosuppression renders the host increased susceptible for secondary infections. It is becoming increasingly clear that not only bacterial sepsis, but also respiratory... (Review)
Review
Immunosuppression renders the host increased susceptible for secondary infections. It is becoming increasingly clear that not only bacterial sepsis, but also respiratory viruses with both severe and mild disease courses such as influenza, respiratory syncytial virus, and the human rhinovirus may induce immunosuppression. In this review, the current knowledge on (mechanisms of) bacterial- and virus-induced immunosuppression and the accompanying susceptibility toward various secondary infections is described. In addition, the frequently encountered secondary pathogens and their preferred localizations are presented. Finally, future perspectives in the context of the development of diagnostic markers and possibilities for personalized therapy to improve the diagnosis and treatment of immunocompromised patients are discussed.
Topics: Coinfection; Humans; Immunocompromised Host; Influenza A virus; Intensive Care Units; Respiratory Syncytial Viruses
PubMed: 27517143
DOI: 10.1097/SHK.0000000000000731 -
Nature Reviews. Microbiology May 2022
Topics: Humans; Respiratory Syncytial Virus Infections; Respiratory Syncytial Virus, Human
PubMed: 35233104
DOI: 10.1038/s41579-022-00717-w -
Viral Immunology Jan 2023Respiratory RNA viruses are a major cause of acute lower respiratory tract infections and contribute substantially to hospitalization among infants, elderly, and... (Review)
Review
Respiratory RNA viruses are a major cause of acute lower respiratory tract infections and contribute substantially to hospitalization among infants, elderly, and immunocompromised. Complete viral clearance from acute infections is not always achieved, leading to persistence. Certain chronic respiratory diseases like asthma and chronic obstructive pulmonary disease have been associated with persistent infection by human respiratory syncytial virus and human rhinovirus, but it is still not clear whether RNA viruses really establish long-term infections as it has been recognized for DNA viruses as human bocavirus and adenoviruses. Herein, we summarize evidence of RNA virus persistence in the human respiratory tract, as well as in some animal models, to highlight how long-term infections might be related to development and/or maintenance of chronic respiratory symptoms.
Topics: Infant; Humans; Aged; Respiratory System; Respiratory Tract Infections; RNA Viruses; Respiratory Syncytial Virus, Human; Asthma
PubMed: 36367976
DOI: 10.1089/vim.2022.0135 -
Cellular and Molecular Life Sciences :... Feb 2024The complement system, a key component of innate immunity, provides the first line of defense against bacterial infection; however, the COVID-19 pandemic has revealed... (Review)
Review
The complement system, a key component of innate immunity, provides the first line of defense against bacterial infection; however, the COVID-19 pandemic has revealed that it may also engender severe complications in the context of viral respiratory disease. Here, we review the mechanisms of complement activation and regulation and explore their roles in both protecting against infection and exacerbating disease. We discuss emerging evidence related to complement-targeted therapeutics in COVID-19 and compare the role of the complement in other respiratory viral diseases like influenza and respiratory syncytial virus. We review recent mechanistic studies and animal models that can be used for further investigation. Novel knockout studies are proposed to better understand the nuances of the activation of the complement system in respiratory viral diseases.
Topics: Animals; Humans; COVID-19; Pandemics; Complement System Proteins; Influenza, Human; Respiratory Syncytial Virus, Human
PubMed: 38368584
DOI: 10.1007/s00018-024-05157-8 -
Expert Review of Vaccines 2023Respiratory syncytial virus (RSV) infection is one of the most common causes of acute respiratory tract infections in young children and the elderly. Infants and young... (Review)
Review
INTRODUCTION
Respiratory syncytial virus (RSV) infection is one of the most common causes of acute respiratory tract infections in young children and the elderly. Infants and young children aged <2 years and the elderly are at particular risk of severe infections requiring hospitalization.
AREAS COVERED
This narrative review summarizes the epidemiology of RSV infection in Korea, with a particular focus on infants and the elderly, where possible, and highlights the need for effective vaccinations against RSV. Relevant papers were identified from a search of PubMed up to December 2021.
EXPERT OPINION
RSV infection is associated with a significant burden of illness in infants and the elderly worldwide and accounts for a substantial number of hospital admissions due to severe lower respiratory tract infections in both of these age groups in Korea. Vaccination has the potential to reduce the burden of acute RSV-associated disease and long-term consequences such as asthma. Increased understanding of the immune response to RSV, including mucosal immunity, and the innate and adaptive immune responses is needed. Technological advances in vaccine platforms could provide better approaches for achieving a safe and effective vaccine-induced immune response.
Topics: Infant; Aged; Child; Humans; Child, Preschool; Respiratory Syncytial Virus Infections; Respiratory Syncytial Virus Vaccines; Immunization; Vaccination; Respiratory Syncytial Viruses; Respiratory Tract Infections; Immunity, Mucosal; Republic of Korea; Respiratory Syncytial Virus, Human
PubMed: 36960592
DOI: 10.1080/14760584.2023.2189459 -
Current Opinion in Infectious Diseases Oct 2021Analyses of the host transcriptional response to infection has proved to be an alternative diagnostic strategy to standard direct pathogen detection. This review... (Review)
Review
PURPOSE OF REVIEW
Analyses of the host transcriptional response to infection has proved to be an alternative diagnostic strategy to standard direct pathogen detection. This review summarizes the value of applying blood and mucosal transcriptome analyses for the diagnosis and management of children with viral and bacterial infections.
RECENT FINDINGS
Over the years, studies have validated the concept that RNA transcriptional profiles derived from children with infectious diseases carry a pathogen-specific biosignature that can be qualitatively and quantitively measured. These biosignatures can be translated into a biologically meaningful context to improve patient diagnosis, as seen in children with tuberculosis, rhinovirus infections, febrile infants and children with pneumonia; understand disease pathogenesis (i.e. congenital CMV) and objectively classify patients according to clinical severity (i.e. respiratory syncytial virus).
SUMMARY
The global assessment of host RNA transcriptional immune responses has improved our understanding of the host-pathogen interactions in the clinical setting. It has shown the potential to be used in clinical situations wherein our current diagnostic tools are inadequate, guiding the diagnosis and classification of children with infectious diseases.
Topics: Bacterial Infections; Biomarkers; Child; Communicable Diseases; Gene Expression Profiling; Humans; Infant; Respiratory Syncytial Virus Infections; Respiratory Syncytial Virus, Human
PubMed: 34232136
DOI: 10.1097/QCO.0000000000000750 -
Journal of Medical Virology Jun 2023In 2022, Austria experienced a severe respiratory syncytial virus (RSV) epidemic with an earlier-than-usual start (Weeks 35/2021-45/2022) and increased numbers of...
In 2022, Austria experienced a severe respiratory syncytial virus (RSV) epidemic with an earlier-than-usual start (Weeks 35/2021-45/2022) and increased numbers of pediatric patients in emergency departments. This surge came 2 years after a season with no cases detected as a result of coronavirus disease 2019 nonpharmaceutical interventions. We analyzed epidemiologic patterns and the phylodynamics of RSV based on approximately 30 800 respiratory specimens collected year-round over 10 years from ambulatory and hospitalized patients from 248 locations in Austria. Genomic surveillance and phylogenetic analysis of 186 RSV-A and 187 RSV-B partial glycoprotein sequences collected from 2018 to 2022 revealed that the 2022/2023 surge was driven by RSV-B in contrast to the surge in the 2021/2022 season that was driven by RSV-A. Whole-genome sequencing and phylodynamic analysis indicated that the RSV-B strain GB5.0.6a was the predominant genotype in the 2022/2023 season and emerged in late 2019. The results provide insight into RSV evolution and epidemiology that will be applicable to future monitoring efforts with the advent of novel vaccines and therapeutics.
Topics: Child; Humans; Austria; COVID-19; Epidemiological Monitoring; Evolution, Molecular; Genotyping Techniques; Molecular Epidemiology; Phylogeny; Respiratory Syncytial Virus Infections; Respiratory Syncytial Viruses; Whole Genome Sequencing
PubMed: 37282809
DOI: 10.1002/jmv.28830 -
Journal of Innate Immunity 2020The impact of respiratory virus infections on the health of children and adults can be very significant. Yet, in contrast to most other childhood infections as well as... (Review)
Review
The impact of respiratory virus infections on the health of children and adults can be very significant. Yet, in contrast to most other childhood infections as well as other viral and bacterial diseases, prophylactic vaccines or effective antiviral treatments against viral respiratory infections are either still not available, or provide only limited protection. Given the widespread prevalence, a general lack of natural sterilizing immunity, and/or high morbidity and lethality rates of diseases caused by influenza, respiratory syncytial virus, coronaviruses, and rhinoviruses, this difficult situation is a genuine societal challenge. A thorough understanding of the virus-host interactions during these respiratory infections will most probably be pivotal to ultimately meet these challenges. This review attempts to provide a comparative overview of the knowledge about an important part of the interaction between respiratory viruses and their host: the arms race between host innate immunity and viral innate immune evasion. Many, if not all, viruses, including the respiratory viruses listed above, suppress innate immune responses to gain a window of opportunity for efficient virus replication and setting-up of the infection. The consequences for the host's immune response are that it is often incomplete, delayed or diminished, or displays overly strong induction (after the delay) that may cause tissue damage. The affected innate immune response also impacts subsequent adaptive responses, and therefore viral innate immune evasion often undermines fully protective immunity. In this review, innate immune responses relevant for respiratory viruses with an RNA genome will briefly be summarized, and viral innate immune evasion based on shielding viral RNA species away from cellular innate immune sensors will be discussed from different angles. Subsequently, viral enzymatic activities that suppress innate immune responses will be discussed, including activities causing host shut-off and manipulation of stress granule formation. Furthermore, viral protease-mediated immune evasion and viral manipulation of the ubiquitin system will be addressed. Finally, perspectives for use of the reviewed knowledge for the development of novel antiviral strategies will be sketched.
Topics: Animals; Coronavirus; Coronavirus Infections; Host Microbial Interactions; Humans; Immunity, Innate; Respiratory Syncytial Virus Infections; Respiratory Syncytial Viruses; Signal Transduction; Virus Internalization; Virus Replication
PubMed: 31610541
DOI: 10.1159/000503030