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Frontiers in Immunology 2022Respiratory tract infections are a leading cause of morbidity and mortality in newborns, infants, and young children. These early life infections present a formidable... (Review)
Review
Respiratory tract infections are a leading cause of morbidity and mortality in newborns, infants, and young children. These early life infections present a formidable immunologic challenge with a number of possibly conflicting goals: simultaneously eliminate the acute pathogen, preserve the primary gas-exchange function of the lung parenchyma in a developing lung, and limit long-term sequelae of both the infection and the inflammatory response. The latter has been most well studied in the context of childhood asthma, where multiple epidemiologic studies have linked early life viral infection with subsequent bronchospasm. This review will focus on the clinical relevance of respiratory syncytial virus (RSV), human metapneumovirus (HMPV), and rhinovirus (RV) and examine the protective and pathogenic host responses within the neonate.
Topics: Child; Child, Preschool; Humans; Immunity; Infant; Infant, Newborn; Metapneumovirus; Respiratory Syncytial Virus, Human; Respiratory Tract Infections; Viruses
PubMed: 35493465
DOI: 10.3389/fimmu.2022.863149 -
The Journal of Infectious Diseases Dec 2022Respiratory syncytial virus (RSV) is an important cause of disease in older adults. We evaluated the safety and immunogenicity of a stabilized RSV prefusion F subunit... (Randomized Controlled Trial)
Randomized Controlled Trial
BACKGROUND
Respiratory syncytial virus (RSV) is an important cause of disease in older adults. We evaluated the safety and immunogenicity of a stabilized RSV prefusion F subunit (RSVpreF) vaccine candidate with/without adjuvant in adults aged 65-85 years.
METHODS
Primary cohort participants were equally randomized to 1 of 7 RSVpreF formulations: 60 µg with either Al(OH)3 or CpG/Al(OH)3, 120 µg with either Al(OH)3 or CpG/Al(OH)3, 240 µg with either Al(OH)3 or CpG/Al(OH)3, 240 µg unadjuvanted, or placebo, administered concomitantly with high-dose seasonal inactivated influenza vaccine (SIIV). Participants in the month 0,2 cohort were randomized to RSVpreF 240 µg with CpG/Al(OH)3 or placebo, administered at months 0 and 2.
RESULTS
All RSVpreF vaccine candidates elicited robust and persistent serum neutralizing responses when administered alone or with SIIV. There was no notable difference in neutralizing response between the formulations, including those containing CpG. In the month 0,2 cohort, there was no booster effect of dose 2. SIIV responses were similar or slightly lower with concomitant administration of RSVpreF. Most systemic and local reactions were mild and more frequent after RSVpreF than placebo.
CONCLUSIONS
RSVpreF formulations were well tolerated and elicited robust neutralizing responses in older adults; however, CpG/Al(OH)3 did not further enhance responses. Clinical Trials Registration. NCT03572062.
Topics: Humans; Aged; Respiratory Syncytial Virus Vaccines; Viral Fusion Proteins; Respiratory Syncytial Virus Infections; Antibodies, Neutralizing; Antibodies, Viral; Respiratory Syncytial Virus, Human; Adjuvants, Immunologic; Adjuvants, Pharmaceutic
PubMed: 35543281
DOI: 10.1093/infdis/jiac189 -
Nature Reviews. Microbiology Feb 2023This study reports that SARS-CoV-2 binds to cilia and reprogrammes microvilli to promote replication in the nasal airway.
This study reports that SARS-CoV-2 binds to cilia and reprogrammes microvilli to promote replication in the nasal airway.
Topics: Mucus; SARS-CoV-2; Cilia; Respiratory Syncytial Virus, Human
PubMed: 36513767
DOI: 10.1038/s41579-022-00842-6 -
Medical Science Monitor : International... Dec 2023In October and November 2023, hospitals in the major cities of Beijing and Liaoning in northern China reported a surge in cases of pneumonia in children, with some...
In October and November 2023, hospitals in the major cities of Beijing and Liaoning in northern China reported a surge in cases of pneumonia in children, with some hospitals being overwhelmed by pediatric emergency admissions. Similar outbreaks of childhood pneumonia had been reported in the autumn of 2022 in Europe and North America. Therefore, increased reports of childhood pneumonia could be driven by post-pandemic changes in the pathogenesis of endemic respiratory infections other than COVID-19, including Mycoplasma pneumoniae, respiratory syncytial virus (RSV), and influenza, rather than emerging novel pathogens. However, the recent reports of increased hospitalizations for children with pneumonia warrant continued infection surveillance and monitoring to exclude new respiratory pathogens or more virulent variants of known pathogens, including SARS-CoV-2. This editorial aims to present what is known about the re-emergence of endemic respiratory infections, which may be the cause of the recently reported outbreaks of childhood pneumonia.
Topics: Humans; Child; Pandemics; Respiratory Tract Infections; Pneumonia; Respiratory Syncytial Virus, Human; Influenza, Human
PubMed: 38037346
DOI: 10.12659/MSM.943312 -
Frontiers in Immunology 2019The pneumoviruses respiratory syncytial virus (RSV) and human metapneumovirus (hMPV) are two widespread human pathogens that can cause severe disease in the young, the... (Review)
Review
The pneumoviruses respiratory syncytial virus (RSV) and human metapneumovirus (hMPV) are two widespread human pathogens that can cause severe disease in the young, the elderly, and the immunocompromised. Despite the discovery of RSV over 60 years ago, and hMPV nearly 20 years ago, there are no approved vaccines for either virus. Antibody-mediated immunity is critical for protection from RSV and hMPV, and, until recently, knowledge of the antibody epitopes on the surface glycoproteins of RSV and hMPV was very limited. However, recent breakthroughs in the recombinant expression and stabilization of pneumovirus fusion proteins have facilitated in-depth characterization of antibody responses and structural epitopes, and have provided an enormous diversity of new monoclonal antibody candidates for therapeutic development. These new data have primarily focused on the RSV F protein, and have led to a wealth of new vaccine candidates in preclinical and clinical trials. In contrast, the major structural antibody epitopes remain unclear for the hMPV F protein. Overall, this review will cover recent advances in characterizing the antigenic sites on the RSV and hMPV F proteins.
Topics: Antibodies, Monoclonal; Antibodies, Viral; Antigens, Viral; Cost of Illness; Epitopes; Global Health; Humans; Pneumovirus; Pneumovirus Infections; Protein Binding; Public Health Surveillance; Respiratory Syncytial Virus Infections; Respiratory Syncytial Virus, Human; Structure-Activity Relationship; Viral Fusion Proteins
PubMed: 31849961
DOI: 10.3389/fimmu.2019.02778 -
Proceedings of the National Academy of... Jan 2023The resolution of infection is an active process with specific molecular and cellular mechanisms that temper inflammation and enhance pathogen clearance. Here, the...
The resolution of infection is an active process with specific molecular and cellular mechanisms that temper inflammation and enhance pathogen clearance. Here, the specialized pro-resolving mediator (SPM) Maresin 1 (MaR1) inhibited respiratory syncytial virus (RSV)-induced inflammation. inlerleukin-13 production from type 2 innate lymphoid cells (ILC) and CD4 T helper type 2 cells was decreased by exogenous MaR1. In addition, MaR1 increased amphiregulin production and decreased RSV viral transcripts to promote resolution. MaR1 also promoted interferon-β production in mouse lung tissues and also in pediatric lung slices. MaR1 significantly inhibited the RSV-triggered aberrant inflammatory phenotype in FoxP3-expressing Tregs. The receptor for MaR1, leucine-rich repeat-containing G protein-coupled receptor 6 (LGR6), was constitutively expressed on Tregs. Following RSV infection, mice lacking Lgr6 had exacerbated type 2 immune responses with an increased viral burden and blunted responses to MaR1. Together, these findings have uncovered a multi-pronged protective signaling axis for MaR1-Lgr6, improving Tregs's suppressive function and upregulating host antiviral genes resulting in decreased viral burden and pathogen-mediated inflammation, ultimately promoting restoration of airway mucosal homeostasis.
Topics: Mice; Animals; Immunity, Innate; Lymphocytes; Inflammation; Respiratory Syncytial Virus Infections; Docosahexaenoic Acids; Pneumonia, Viral; Respiratory Syncytial Virus, Human; Receptors, G-Protein-Coupled
PubMed: 36595677
DOI: 10.1073/pnas.2206480120 -
Archivos de Bronconeumologia Apr 2022
Topics: Humans; Infant; Respiratory Syncytial Virus, Human
PubMed: 34226785
DOI: 10.1016/j.arbres.2021.06.007 -
Frontiers in Immunology 2023Respiratory syncytial virus (RSV) and Rhinovirus (RV) infections are major triggers of severe lower respiratory illnesses (sLRI) in infants and children and are strongly...
Respiratory syncytial virus (RSV) and Rhinovirus (RV) infections are major triggers of severe lower respiratory illnesses (sLRI) in infants and children and are strongly associated with the subsequent development of asthma. Decades of research has focused on the role of type I interferons in antiviral immunity and ensuing airway diseases, however, recent findings have highlighted several novel aspects of the interferon response that merit further investigation. In this perspective, we discuss emerging roles of type I interferons in the pathogenesis of sLRI in children. We propose that variations in interferon response patterns exist as discrete endotypes, which operate locally in the airways and systemically through a lung-blood-bone marrow axis. We discuss new insights into the role of interferons in immune training, bacterial lysate immunotherapy, and allergen-specific immunotherapy. Interferons play complex and diverse roles in the pathogenesis of sLRI and later asthma, providing new directions for mechanistic studies and drug development.
Topics: Infant; Child; Humans; Asthma; Antiviral Agents; Respiratory Syncytial Virus, Human; Interferon Type I; Virus Diseases
PubMed: 36895568
DOI: 10.3389/fimmu.2023.1109001 -
Vaccine Nov 2023Respiratory syncytial virus (RSV) is the predominant cause of acute lower respiratory infection (ALRI) in young children worldwide, yet no licensed RSV vaccine exists to...
Respiratory syncytial virus (RSV) is the predominant cause of acute lower respiratory infection (ALRI) in young children worldwide, yet no licensed RSV vaccine exists to help prevent the millions of illnesses and hospitalizations and tens of thousands of young lives taken each year. Monoclonal antibody (mAb) prophylaxis exists for prevention of RSV in a small subset of very high-risk infants and young children, but the only currently licensed product is impractical, requiring multiple doses and expensive for the low-income settings where the RSV disease burden is greatest. A robust candidate pipeline exists to one day prevent RSV disease in infant and pediatric populations, and it focuses on two promising passive immunization approaches appropriate for low-income contexts: maternal RSV vaccines and long-acting infant mAbs. Licensure of one or more candidates is feasible over the next one to three years and, depending on final product characteristics, current economic models suggest both approaches are likely to be cost-effective. Strong coordination between maternal and child health programs and the Expanded Program on Immunization will be needed for effective, efficient, and equitable delivery of either intervention. This 'Vaccine Value Profile' (VVP) for RSV is intended to provide a high-level, holistic assessment of the information and data that are currently available to inform the potential public health, economic and societal value of pipeline vaccines and vaccine-like products. This VVP was developed by a working group of subject matter experts from academia, non-profit organizations, public private partnerships and multi-lateral organizations, and in collaboration with stakeholders from the WHO headquarters. All contributors have extensive expertise on various elements of the RSV VVP and collectively aimed to identify current research and knowledge gaps. The VVP was developed using only existing and publicly available information.
Topics: Infant; Child; Humans; Child, Preschool; Respiratory Syncytial Virus Vaccines; Antibodies, Monoclonal; Respiratory Syncytial Virus Infections; Respiratory Syncytial Virus, Human; Immunization, Passive; Respiratory Tract Infections
PubMed: 37422378
DOI: 10.1016/j.vaccine.2022.09.081 -
Cells Mar 2022Despite over half a century of research, respiratory syncytial virus (RSV)-induced bronchiolitis remains a major cause of hospitalisation in infancy, while vaccines and... (Review)
Review
Despite over half a century of research, respiratory syncytial virus (RSV)-induced bronchiolitis remains a major cause of hospitalisation in infancy, while vaccines and specific therapies still await development. Our understanding of mucosal immune responses to RSV continues to evolve, but recent studies again highlight the role of Type-2 immune responses in RSV disease and hint at the possibility that it dampens Type-1 antiviral immunity. Other immunoregulatory pathways implicated in RSV disease highlight the importance of focussing on localised mucosal responses in the respiratory mucosa, as befits a virus that is essentially confined to the ciliated respiratory epithelium. In this review, we discuss studies of mucosal immune cell infiltration and production of inflammatory mediators in RSV bronchiolitis and relate these studies to observations from peripheral blood. We also discuss the advantages and limitations of studying the nasal mucosa in a disease that is most severe in the lower airway. A fresh focus on studies of RSV pathogenesis in the airway mucosa is set to revolutionise our understanding of this common and important infection.
Topics: Bronchiolitis; Humans; Immunity, Mucosal; Nasal Mucosa; Respiratory Syncytial Virus Infections; Respiratory Syncytial Virus, Human
PubMed: 35406717
DOI: 10.3390/cells11071153