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The Lancet. Microbe Sep 2023Human metapneumovirus (hMPV) is one of the leading causes of respiratory infection. Since its discovery in 2001, no specific antiviral or vaccine has been available in... (Review)
Review
Human metapneumovirus (hMPV) is one of the leading causes of respiratory infection. Since its discovery in 2001, no specific antiviral or vaccine has been available in contrast to its closely related family member human respiratory syncytial virus (hRSV). Neutralising monoclonal antibodies (nMAbs) are the core effectors of vaccines and are essential therapeutic immune drugs against infectious pathogens. The development of nMAbs against hMPV has accelerated in recent years as a result of breakthroughs in viral fusion (F) protein structural biology and experience with hRSV and other enveloped viruses. We provide an overview of the potent F-specific nMAbs of hMPV, generalise their targeting F antigen epitopes, and discuss the nMAb development strategy and future directions for hMPV and broad-spectrum hMPV, hRSV nMabs, and vaccine research and development.
PubMed: 37499668
DOI: 10.1016/S2666-5247(23)00134-9 -
Infectious Disease Clinics of North... Mar 2024Viral pneumonia is usually community acquired and caused by influenza, parainfluenza, respiratory syncytial virus, human metapneumovirus, and adenovirus. Many of these... (Review)
Review
Viral pneumonia is usually community acquired and caused by influenza, parainfluenza, respiratory syncytial virus, human metapneumovirus, and adenovirus. Many of these infections are airway centric and chest imaging demonstrates bronchiolitis and bronchopneumonia, With the exception of adenovirus infections, the presence of lobar consolidation usually suggests bacterial coinfection. Community-acquired viral pathogens can cause more severe pneumonia in immunocompromised hosts, who are also susceptible to CMV and varicella infection. These latter 2 pathogens are less likely to manifest the striking airway-centric pattern. Airway-centric pattern is distinctly uncommon in Hantavirus pulmonary syndrome, a rare environmentally acquired infection with high mortality.
Topics: Humans; Tomography, X-Ray Computed; Pneumonia, Viral; Influenza, Human; Paramyxoviridae Infections; Metapneumovirus; Adenoviridae Infections; Community-Acquired Infections; Respiratory Tract Infections
PubMed: 38280762
DOI: 10.1016/j.idc.2023.12.009 -
Current Opinion in Virology Aug 2023Respiratory syncytial virus (RSV) and human metapneumovirus (hMPV) continue to be a global burden to infants, the elderly, and immunocompromised individuals. In the past... (Review)
Review
Respiratory syncytial virus (RSV) and human metapneumovirus (hMPV) continue to be a global burden to infants, the elderly, and immunocompromised individuals. In the past ten years, there has been substantial progress in the development of new vaccine candidates and therapies against these viruses. These advancements were guided by the structural elucidation of the major surface glycoproteins for these viruses, the fusion (F) protein and attachment (G) protein. The identification of immunodominant epitopes on the RSV F and hMPV F proteins has expanded current knowledge on antibody-mediated immune responses, which has led to new approaches for vaccine and therapeutic development through the stabilization of pre-fusion constructs of the F protein and pre-fusion-specific monoclonal antibodies with high potency and efficacy. In this review, we describe structural characteristics of known antigenic sites on the RSV and hMPV proteins, their influence on the immune response, and current progress in vaccine and therapeutic development.
Topics: Humans; Aged; Metapneumovirus; Antibodies, Viral; Antibodies, Neutralizing; Viral Fusion Proteins; Respiratory Syncytial Virus, Human; Respiratory Syncytial Virus Infections
PubMed: 37544710
DOI: 10.1016/j.coviro.2023.101337 -
Current Opinion in Infectious Diseases Oct 2023The successes of the coronavirus disease 2019 (COVID-19) mRNA vaccines have accelerated the development of mRNA vaccines against other respiratory pathogens. The aim of... (Review)
Review
PURPOSE OF REVIEW
The successes of the coronavirus disease 2019 (COVID-19) mRNA vaccines have accelerated the development of mRNA vaccines against other respiratory pathogens. The aim of this review is to highlight COVID-19 mRNA vaccine advances and provide an update on the progress of mRNA vaccine development against other respiratory pathogens.
RECENT FINDINGS
The COVID-19 mRNA vaccines demonstrated effectiveness in preventing severe COVID-19 and death. H7N9 and H10N8 avian influenza mRNA vaccines have demonstrated safety and immunogenicity in phase 1 clinical trials. Numerous seasonal influenza mRNA vaccines are in phase 1-3 clinical trials. Respiratory syncytial virus (RSV) mRNA vaccines have progressed to phase 2-3 clinical trials in adults and a phase 1 clinical trial in children. A combined human metapneumovirus and parainfluenza-3 mRNA vaccines was found to be well tolerated and immunogenic in a phase 1 trial among adults and trials are being conducted among children. Clinical trials of mRNA vaccines combining antigens from multiple respiratory viruses are underway.
SUMMARY
The development of mRNA vaccines against respiratory viruses has progressed rapidly in recent years. Promising vaccine candidates are moving through the clinical development pathway to test their efficacy in preventing disease against respiratory viral pathogens.
Topics: Adult; Child; Animals; Humans; COVID-19 Vaccines; Influenza A Virus, H7N9 Subtype; Antibodies, Viral; COVID-19; Influenza Vaccines; Respiratory Syncytial Virus Vaccines; Influenza in Birds; Respiratory Syncytial Virus Infections
PubMed: 37462930
DOI: 10.1097/QCO.0000000000000948 -
Cell Host & Microbe Aug 2023Respiratory syncytial virus (RSV) and human metapneumovirus (hMPV) infections pose a significant health burden. Using pre-fusion conformation fusion (F) proteins, we...
Respiratory syncytial virus (RSV) and human metapneumovirus (hMPV) infections pose a significant health burden. Using pre-fusion conformation fusion (F) proteins, we isolated a panel of anti-F antibodies from a human donor. One antibody (RSV-199) potently cross-neutralized 8 RSV and hMPV strains by recognizing antigenic site III, which is partially conserved in RSV and hMPV F. Next, we determined the cryoelectron microscopy (cryo-EM) structures of RSV-199 bound to RSV F trimers, hMPV F monomers, and an unexpected dimeric form of hMPV F. These structures revealed how RSV-199 engages both RSV and hMPV F proteins through conserved interactions of the antibody heavy-chain variable region and how variability within heavy-chain complementarity-determining region 3 (HCDR3) can be accommodated at the F protein interface in site-III-directed antibodies. Furthermore, RSV-199 offered enhanced protection against RSV A and B strains and hMPV in cotton rats. These findings highlight the mechanisms of broad neutralization and therapeutic potential of RSV-199.
Topics: Humans; Metapneumovirus; Antibodies, Neutralizing; Antibodies, Viral; Cryoelectron Microscopy; Respiratory Syncytial Virus, Human; Immunoglobulin Variable Region; Viral Fusion Proteins
PubMed: 37516111
DOI: 10.1016/j.chom.2023.07.002 -
The Journal of Infection Aug 2023Human metapneumovirus (HMPV) is an important aetiologic agent of respiratory tract infection (RTI). This study aimed to describe the prevalence, genetic diversity, and...
BACKGROUND
Human metapneumovirus (HMPV) is an important aetiologic agent of respiratory tract infection (RTI). This study aimed to describe the prevalence, genetic diversity, and evolutionary dynamics of HMPV.
METHODS
Laboratory-confirmed HMPV were characterised based on partial-coding G gene sequences with MEGA.v6.0. WGS was performed with Illumina, and evolutionary analyses with Datamonkey and Nextstrain.
RESULTS
HMPV prevalence was 2.5%, peaking in February-April and with an alternation in the predominance of HMPV-A and -B until the emergence of SARS-CoV-2, not circulating until summer and autumn-winter 2021, with a higher prevalence and with the almost only circulation of A2c. G and SH proteins were the most variable, and 70% of F protein was under negative selection. Mutation rate of HMPV genome was 6.95 × 10 substitutions/site/year.
CONCLUSION
HMPV showed a significant morbidity until the emergence of SARS-CoV-2 pandemic in 2020, not circulating again until summer and autumn 2021, with a higher prevalence and with almost the only circulation of A2c, probably due to a more efficient immune evasion mechanism. The F protein showed a very conserved nature, supporting the need for steric shielding. The tMRCA showed a recent emergence of the A2c variants carrying duplications, supporting the importance of virological surveillance.
Topics: Humans; Infant; Metapneumovirus; Paramyxoviridae Infections; Spain; Genotype; COVID-19; SARS-CoV-2; Respiratory Tract Infections; Phylogeny
PubMed: 37178807
DOI: 10.1016/j.jinf.2023.05.004 -
Journal of Asthma and Allergy 2023Asthma is a common airway disease, affecting millions of people worldwide. Although most asthma patients experience mild symptoms, it is characterized by variable... (Review)
Review
Asthma is a common airway disease, affecting millions of people worldwide. Although most asthma patients experience mild symptoms, it is characterized by variable airflow limitation, which can occasionally become life threatening in the case of a severe exacerbation. The commonest triggers of asthma exacerbations in both children and adults are viral infections. In this review article, we will try to investigate the most common viruses triggering asthma exacerbations and their role in asthma immunopathogenesis, since viral infections in young adults are thought to trigger the development of asthma either right away after the infection or at a later stage of their life. The commonest viral pathogens associated with asthma include the respiratory syncytial virus, rhinoviruses, influenza and parainfluenza virus, metapneumovirus and coronaviruses. All these viruses exploit different molecular pathways to infiltrate the host. Asthmatics are more prone to severe viral infections due to their unique inflammatory response, which is mostly characterized by T2 cytokines. Unlike the normal T1 high response to viral infection, asthmatics with T2 high inflammation are less potent in containing a viral infection. Inhaled and/or systematic corticosteroids and bronchodilators remain the cornerstone of asthma exacerbation treatment, and although many targeted therapies which block molecules that viruses use to infect the host have been used in a laboratory level, none has been yet approved for clinical use. Nevertheless, further understanding of the unique pathway that each virus follows to infect an individual may be crucial in the development of targeted therapies for the commonest viral pathogens to effectively prevent asthma exacerbations. Finally, biologic therapies resulted in a complete change of scenery in the treatment of severe asthma, especially with a T2 high phenotype. All available data suggest that monoclonal antibodies are safe and able to drastically reduce the rate of viral asthma exacerbations.
PubMed: 37791040
DOI: 10.2147/JAA.S277455 -
The Pediatric Infectious Disease Journal Nov 2023Human metapneumovirus (HMPV) and respiratory syncytial virus (RSV) are 2 common causes of acute respiratory tract infections in infants and young children. The objective...
BACKGROUND
Human metapneumovirus (HMPV) and respiratory syncytial virus (RSV) are 2 common causes of acute respiratory tract infections in infants and young children. The objective of this study is to compare the demographics and outcomes of children hospitalized with HMPV and RSV infections in the United States.
METHODS
We performed a retrospective cohort analysis of children 1 month to less than 3 years old discharged during 2016 with HMPV or RSV infection using the Kids' Inpatient Database. Children with HMPV and RSV coinfection were excluded. Data were weighted for national estimates.
RESULTS
There were 6585 children with HMPV infection and 70,824 with RSV infection discharged during the study period. The mean age of children with HMPV infection was higher than that of children with RSV infection (0.73 ± 0.8 vs. 0.42 ± 0.7 years; P < 0.05). The mortality rate was significantly higher in children with the presence of any complex chronic conditions compared to those without, in both HMPV [odds ratio (OR): 32.42; CI: 9.931-105.857; P < 0.05] as well as RSV (OR: 35.81; CI: 21.12-57.97; P < 0.05) groups. The adjusted median length of stay was longer (4.64 days; CI: 4.52-4.76 days vs. 3.33 days; CI: 3.31-3.35 days; P < 0.001) and total charges were higher ($44,358; CI: $42,145-$46,570 vs. $22,839; CI: $22,512-$23,166; P < 0.001), with HMPV infection. The mortality rate was similar in HMPV infection compared to RSV infection on multivariable analysis (OR: 1.48; P > 0.05).
CONCLUSION
In hospitalized children in the United States, HMPV infection is less common than RSV infection. Complex chronic conditions are more prevalent in children hospitalized with HMPV infection. Hospitalization with HMPV is associated with longer length of stay and higher hospital charges. The adjusted mortality is similar with both infections.
PubMed: 37523504
DOI: 10.1097/INF.0000000000004055