scholarly journals Respiratory Syncytial Virus Infection: Immune Response, Immunopathogenesis, and Treatment

1999 ◽  
Vol 12 (2) ◽  
pp. 298-309 ◽  
Author(s):  
Joseph B. Domachowske ◽  
Helene F. Rosenberg
Keyword(s):  
Immune Response ◽  
Respiratory Syncytial Virus ◽  
Respiratory Tract ◽  
Neutralizing Antibodies ◽  
Lower Respiratory Tract ◽  
Immunoglobulin E ◽  
Neutralizing Antibody ◽  
Rsv Infection ◽  
Syncytial Virus

SUMMARY Respiratory syncytial virus (RSV) is the single most important cause of lower respiratory tract infection during infancy and early childhood. Once RSV infection is established, the host immune response includes the production of virus-neutralizing antibodies and T-cell-specific immunity. The humoral immune response normally results in the development of anti-RSV neutralizing-antibody titers, but these are often suboptimal during an infant’s initial infection. Even when the production of RSV neutralizing antibody following RSV infection is robust, humoral immunity wanes over time. Reinfection during subsequent seasons is common. The cellular immune response to RSV infection is also important for the clearance of virus. This immune response, vital for host defense against RSV, is also implicated in the immunopathogenesis of severe lower respiratory tract RSV bronchiolitis. Many details of the immunology and immunopathologic mechanisms of RSV disease known at present have been learned from rodent models of RSV disease and are discussed in some detail. In addition, the roles of immunoglobulin E, histamine, and eosinophils in the immunopathogenesis of RSV disease are considered. Although the treatment of RSV bronchiolitis is primarily supportive, the role of ribavirin is briefly discussed. Novel approaches to the development of new antiviral drugs with promising anti-RSV activity in vitro are also described.

Reappraisal of respiratory syncytial virus as an aetiology of severe acute lower respiratory tract infections in children younger than 5 years in Nigeria

2019 ◽  
Vol 113 (8) ◽  
pp. 446-452
Author(s):  
Damilola M Oladele ◽  
Dimeji P Oladele ◽  
Rasheedat M Ibraheem ◽  
Mohammed B Abdulkadir ◽  
Rasaki Adewole Raheem ◽  
...  
Keyword(s):  
Respiratory Syncytial Virus ◽  
Respiratory Tract ◽  
Lower Respiratory Tract ◽  
Respiratory Tract Infections ◽  
Preventive Strategy ◽  
Lower Respiratory Tract Infections ◽  
Cross Sectional ◽  
Rsv Infection ◽  
Syncytial Virus ◽  
Tract Infections

Abstract Background Acute lower respiratory tract infections (ALRIs) especially severe ALRIs, constitute a global high burden of morbidity and mortality in children <5 y of age and respiratory syncytial virus (RSV) has been documented to a play a major aetiological role. However, Nigerian reports on severe childhood RSV ALRIs are rare and most reports are old. With recent advances in RSV preventive strategy, arises the need for a recent appraisal of RSV infection in children with severe ALRI. The current study thus set out to determine the prevalence of RSV infection among hospitalized children <5 y of age and describe the related social determinants. Methods We performed a descriptive cross-sectional study conducted over 1 y of 120 children, ages 2–59 months, diagnosed with ALRI. Relevant data were obtained and an antigen detection assay was used for viral studies. Results The prevalence of RSV infection was 34.2% and its peak was in the rainy months. The proportion of infants in the RSV-positive group was significantly higher than that in the RSV-negative group (82.9% vs 54.4%; p=0.002). These findings were largely consistent with those of earlier reports. Conclusions RSV has remained a common cause of severe ALRI in infants, especially during the rainy months in Nigeria. It is thus suggested that more effort be focused towards implementing the current global recommendations for the prevention of RSV-associated LRI, particularly in infants.

scholarly journals The Human Immune Response to Respiratory Syncytial Virus Infection

2017 ◽  
Vol 30 (2) ◽  
pp. 481-502 ◽  
Author(s):  
Clark D. Russell ◽  
Stefan A. Unger ◽  
Marc Walton ◽  
Jürgen Schwarze
Keyword(s):  
Immune Response ◽  
Respiratory Syncytial Virus ◽  
T Cell ◽  
T Cell Response ◽  
Rsv Infection ◽  
Human Immune Response ◽  
Ifn Γ ◽  
Human Immune ◽  
Syncytial Virus

SUMMARY Respiratory syncytial virus (RSV) is an important etiological agent of respiratory infections, particularly in children. Much information regarding the immune response to RSV comes from animal models and in vitro studies. Here, we provide a comprehensive description of the human immune response to RSV infection, based on a systematic literature review of research on infected humans. There is an initial strong neutrophil response to RSV infection in humans, which is positively correlated with disease severity and mediated by interleukin-8 (IL-8). Dendritic cells migrate to the lungs as the primary antigen-presenting cell. An initial systemic T-cell lymphopenia is followed by a pulmonary CD8+ T-cell response, mediating viral clearance. Humoral immunity to reinfection is incomplete, but RSV IgG and IgA are protective. B-cell-stimulating factors derived from airway epithelium play a major role in protective antibody generation. Gamma interferon (IFN-γ) has a strongly protective role, and a Th2-biased response may be deleterious. Other cytokines (particularly IL-17A), chemokines (particularly CCL-5 and CCL-3), and local innate immune factors (including cathelicidins and IFN-λ) contribute to pathogenesis. In summary, neutrophilic inflammation is incriminated as a harmful response, whereas CD8+ T cells and IFN-γ have protective roles. These may represent important therapeutic targets to modulate the immunopathogenesis of RSV infection.

Outbreak of Nosocomial Respiratory Syncytial Virus Infections in a Hematology and Transplant Unit.

Blood ◽  
2012 ◽  
Vol 120 (21) ◽  
pp. 3032-3032
Author(s):  
Nicola Lehners ◽  
Paul Schnitzler ◽  
Gerlinde Egerer ◽  
Peter Dreger ◽  
Christoph Eisenbach ◽  
...  
Keyword(s):  
Respiratory Syncytial Virus ◽  
Sequence Analysis ◽  
Respiratory Tract ◽  
Lower Respiratory Tract ◽  
Outbreak Strain ◽  
Major Mode ◽  
Rsv Infection ◽  
Tract Involvement ◽  
Syncytial Virus ◽  
Respiratory Specimens

Abstract Abstract 3032 Respiratory syncytial virus (RSV) is a pathogen associated with bronchiolitis in infants and small children. However, immunocompromised adults might also be at risk for severe lower respiratory tract involvement induced by RSV. We report the rapid control of an outbreak of nosocomial RSV infections in an institution with special focus on allogeneic and autologous stem cell transplantations. Between November 2011 and March 2012 56 patients were diagnosed with RSV infection by RT-PCR at our institution. In order to identify possible risk factors for lower respiratory tract involvement in RSV infected patients, clinical course of infection as well as radiological and laboratory findings were evaluated. Characterization of RSV strains in respiratory specimens was achieved by sequence analysis of part of the RSV glycoprotein G gene and phylogenetic comparison of outbreak and community strains was performed. Out of 56 patients with RSV infection, 39 patients showed signs of lower respiratory tract involvement. 14 fatal outcomes were observed. In most of the lethal cases coinfections with other pathogens such as Aspergillus spp. or Pseudomonas aeruginosa were present. Therefore the exact impact of RSV on the fatal outcome remains difficult, if not impossible, to assess. Age, sex, underlying disease, disease control or transplant status did not differ significantly between severe and non-severe cases. However, hypogammaglobulinemia was associated with a higher risk for fatal infection (p = 0.03) in univariate analysis, whereas therapy with oral ribavirin might show a protective effect (p = 0.02). Prolonged viral shedding was frequently observed (median 22.5 [1 – 143] days), most pronounced in patients folllowing allogeneic transplantation (p = 0.04). The major mode of RSV transmission seemed to be direct patient-to-patient contact as suggested by evaluation of patient movements on the wards. Sequence analysis on respiratory specimens obtained from 46 patients revealed the presence of a particular outbreak strain in 40 patients, characterized by an identical nucleotide sequence of RSV GA2 subtype. Phylogenetic analysis showed low prevalence of the outbreak strain in the community. By implementation of rigorous isolation measures containment of outbreak was achieved. Highly contagious viral pathogens such as RSV are able to cause rapidly spreading outbreaks among immunocompromised patients. Hypogammaglobulinemia might be a risk factor for severe lower respiratory tract infection. Treatment with oral ribavirin might have a positive effect on outcome. Rigorous isolation measures are essential to the containment of outbreak. Disclosures: Off Label Use: ribavirin aerosol is FDA approved for severe cases of RSV in infants and young children.

Serious Respiratory Tract Disease Caused by Respiratory Syncytial Virus: Prospects for Improved Therapy and Effective Immunization

PEDIATRICS ◽  
1992 ◽  
Vol 90 (1) ◽  
pp. 137-143
Author(s):  
Robert M. Chanock ◽  
Robert H. Parrott ◽  
Mark Connors ◽  
Peter L. Collins ◽  
Brian R. Murphy
Keyword(s):  
Respiratory Syncytial Virus ◽  
Respiratory Tract ◽  
Lower Respiratory Tract ◽  
Durable Resistance ◽  
Secretory Iga ◽  
Upper Respiratory Tract ◽  
Viral Pathogen ◽  
Rsv Infection ◽  
Upper Respiratory ◽  
Syncytial Virus

On this felicitous occasion we honor Dr Saul Krugman for his many contributions to the study and control of a wide variety of important pediatric viral diseases. In preparing our remarks we found it difficult to identify a major pediatric viral pathogen upon which Saul had not left his mark. One of the few that escaped, for reasons unknown, is respiratory syncytial virus (RSV). Since RSV is the major pediatric respiratory tract viral pathogen, we thought this agent might pique his interest. Those of us studying RSV need all the help we can receive from biomedical scientists of Saul's caliber. What follows is a summary of current efforts to develop improved therapy and effective immunoprophylaxis for this elusive respiratory tract viral pathogen. IMMUNITY TO RSV DISEASE The mechanisms by which the immune system protects the respiratory tract against RSV infection and disease are not completely understood. However, it is clear that infection (or reinfection) induces resistance in the upper respiratory tract that is neither complete nor long lasting.1,2 The situation is some-what more favorable in the lower respiratory tract, where infection (or reinfection) induces more substantial and more durable resistance to disease. As a consequence, cumulative immunity from multiple reinfections protects older children and adults against the more serious forms of disease involving the lower respiratory tract such as bronchiolitis and pneumonia. Resistance to RSV infection in the upper respiratory tract appears to be mediated primarily by local secretory IgA antibodies, which explains the transitory nature of immunity in this region.3

scholarly journals Presumed Risk Factors and Biomarkers for Severe Respiratory Syncytial Virus Disease and Related Sequelae: Protocol for an Observational Multicenter, Case-Control Study From the Respiratory Syncytial Virus Consortium in Europe (RESCEU)

2020 ◽  
Vol 222 (Supplement_7) ◽  
pp. S658-S665 ◽  
Author(s):  
Kimberley Jefferies ◽  
Simon B Drysdale ◽  
Hannah Robinson ◽  
Elizabeth Ann Clutterbuck ◽  
Luke Blackwell ◽  
...  
Keyword(s):  
Risk Factors ◽  
Respiratory Syncytial Virus ◽  
Tract Infection ◽  
Respiratory Tract ◽  
Respiratory Tract Infection ◽  
Disease Severity ◽  
Lower Respiratory Tract ◽  
Viral Pathogen ◽  
Rsv Infection ◽  
Syncytial Virus

Abstract Respiratory syncytial virus (RSV) is the leading viral pathogen associated with acute lower respiratory tract infection and hospitalization in children &lt; 5 years of age worldwide. While there are known clinical risk factors for severe RSV infection, the majority of those hospitalized are previously healthy infants. There is consequently an unmet need to identify biomarkers that predict host response, disease severity, and sequelae. The primary objective is to identify biomarkers of severe RSV acute respiratory tract infection (ARTI) in infants. Secondary objectives include establishing biomarkers associated with respiratory sequelae following RSV infection and characterizing the viral load, RSV whole-genome sequencing, host immune response, and transcriptomic, proteomic, metabolomic and epigenetic signatures associated with RSV disease severity. Six hundred thirty infants will be recruited across 3 European countries: the Netherlands, Spain, and the United Kingdom. Participants will be recruited into 2 groups: (1) infants with confirmed RSV ARTI (includes upper and lower respiratory tract infections), 500 without and 50 with comorbidities; and (2) 80 healthy controls. At baseline, participants will have nasopharyngeal, blood, buccal, stool, and urine samples collected, plus complete a questionnaire and 14-day symptom diary. At convalescence (7 weeks ± 1 week post-ARTI), specimen collection will be repeated. Laboratory measures will be correlated with symptom severity scores to identify corresponding biomarkers of disease severity. Clinical Trials Registration NCT03756766.

scholarly journals A Peptide Mimic of a Protective Epitope of Respiratory Syncytial Virus Selected from a Combinatorial Library Induces Virus-Neutralizing Antibodies and Reduces Viral Load In Vivo

1998 ◽  
Vol 72 (3) ◽  
pp. 2040-2046 ◽  
Author(s):  
Daniel Chargelegue ◽  
Obeid E. Obeid ◽  
Shiou-Chih Hsu ◽  
Michael D. Shaw ◽  
Andrew N. Denbury ◽  
...  
Keyword(s):  
Respiratory Syncytial Virus ◽  
Neutralizing Antibodies ◽  
Solid Phase ◽  
Effective Vaccine ◽  
Peptide Mimic ◽  
Rsv Infection ◽  
Multiple Antigen Peptides ◽  
Syncytial Virus

ABSTRACT Respiratory syncytial virus (RSV) is the most important cause of bronchiolitis and pneumonia in infants and young children worldwide. As yet, there is no effective vaccine against RSV infection, and previous attempts to develop a formalin-inactivated vaccine resulted in exacerbated disease in recipients subsequently exposed to the virus. In the work described here, a combinatorial solid-phase peptide library was screened with a protective monoclonal antibody (MAb 19) to identify peptide mimics (mimotopes) of a conserved and conformationally-determined epitope of RSV fusion (F) protein. Two sequences identified (S1 [HWYISKPQ] and S2 [HWYDAEVL]) reacted specifically with MAb 19 when they were presented as solid-phase peptides. Furthermore, after amino acid substitution analyses, three sequences derived from S1 (S1S [HWSISKPQ], S1K [KWYISKPQ], and S1P [HPYISKPQ]), presented as multiple antigen peptides (MAPs), also showed strong reactivity with MAb 19. The affinity constants of the binding of MAb 19, determined by surface plasmon resonance analyses, were 1.19 × 109 and 4.93 × 109 M−1 for S1 and S1S, respectively. Immunization of BALB/c mice with these mimotopes, presented as MAPs, resulted in the induction of anti-peptide antibodies that inhibited the binding of MAb 19 to RSV and neutralized viral infection in vitro, with titers equivalent to those in sera from RSV-infected animals. Following RSV challenge of S1S mimotope-immunized mice, a 98.7% reduction in the titer of virus in the lungs was observed. Furthermore, there was a greatly reduced cell infiltration in the lungs of immunized mice compared to that in controls. These results indicate the potential of peptide mimotopes to protect against RSV infection without exacerbating pulmonary pathology.

scholarly journals Isolation and Characterization of Monoclonal Antibodies Which Neutralize Human Metapneumovirus In Vitro and In Vivo

2006 ◽  
Vol 80 (16) ◽  
pp. 7799-7806 ◽  
Author(s):  
Nancy D. Ulbrandt ◽  
Hong Ji ◽  
Nita K. Patel ◽  
Jeffrey M. Riggs ◽  
Yambasu A. Brewah ◽  
...  
Keyword(s):  
Monoclonal Antibody ◽  
Monoclonal Antibodies ◽  
Respiratory Tract ◽  
Neutralizing Antibodies ◽  
Lower Respiratory Tract ◽  
Human Metapneumovirus ◽  
F Protein ◽  
Isolation And Characterization ◽  
Syncytial Virus

ABSTRACT Human metapneumovirus (hMPV) is a recently described member of the Paramyxoviridae family/Pneumovirinae subfamily and shares many common features with respiratory syncytial virus (RSV), another member of the same subfamily. hMPV causes respiratory tract illnesses that, similar to human RSV, occur predominantly during the winter months and have symptoms that range from mild to severe cough, bronchiolitis, and pneumonia. Like RSV, the hMPV virus can be subdivided into two genetic subgroups, A and B. With RSV, a single monoclonal antibody directed at the fusion (F) protein can prevent severe lower respiratory tract RSV infection. Because of the high level of sequence conservation of the F protein across all the hMPV subgroups, this protein is likely to be the preferred antigenic target for the generation of cross-subgroup neutralizing antibodies. Here we describe the generation of a panel of neutralizing monoclonal antibodies that bind to the hMPV F protein. A subset of these antibodies has the ability to neutralize prototypic strains of both the A and B hMPV subgroups in vitro. Two of these antibodies exhibited high-affinity binding to the F protein and were shown to protect hamsters against infection with hMPV. The data suggest that a monoclonal antibody could be used prophylactically to prevent lower respiratory tract disease caused by hMPV.

Factors associated with severe respiratory syncytial virus disease in hospitalised children: a retrospective analysis

2021 ◽  
pp. archdischild-2021-322435
Author(s):  
Jeremy Anderson ◽  
Michelle Oeum ◽  
Eva Verkolf ◽  
Paul V Licciardi ◽  
Kim Mulholland ◽  
...  
Keyword(s):  
Respiratory Syncytial Virus ◽  
Tract Infection ◽  
Respiratory Tract ◽  
Respiratory Tract Infection ◽  
Lower Respiratory Tract ◽  
Severe Disease ◽  
Severe Respiratory Syncytial Virus ◽  
Factors Associated ◽  
Rsv Infection ◽  
Syncytial Virus

BackgroundEarly recognition of children at risk of severe respiratory syncytial virus (RSV) lower respiratory tract infection is important as it informs management decisions. We aimed to evaluate factors associated with severe disease among young children hospitalised with RSV infection.MethodsWe conducted a retrospective cohort study of all children <2 years of age hospitalised for RSV lower respiratory tract infection at a single tertiary paediatric hospital over three RSV seasons (January 2017–December 2019). We classified children as having ‘moderate’ or ‘severe’ disease based on the level of respiratory intervention and used univariable and multivariable regression models to determine factors associated with severe disease.ResultsOf 970 hospitalised children, 386 (40%) were classified as having ‘severe’ and 584 (60%) as having ‘moderate’ RSV disease. On multivariable analyses, age <2 months (OR: 2.3, 95% CI 1.6 to 3.3, p<0.0001), prematurity (OR: 1.6, 95% CI 1.1 to 2.4, p=0.02) and RSV–parainfluenza virus type 3 (PIV3) codetection (OR: 2.6, 95% CI 1.05 to 6.5, p=0.04) were independently associated with severe disease.ConclusionYounger age, prematurity and PIV3 codetection were associated with severe RSV disease in children <2 years of age hospitalised with RSV infection. The association between PIV3 and severe RSV disease is a novel finding and warrants further investigation.

scholarly journals Immunogenicity of RSV F DNA Vaccine in BALB/c Mice

2016 ◽  
Vol 2016 ◽  
pp. 1-10 ◽  
Author(s):  
Erdal Eroglu ◽  
Ankur Singh ◽  
Swapnil Bawage ◽  
Pooja M. Tiwari ◽  
Komal Vig ◽  
...  
Keyword(s):  
Immune Response ◽  
Dna Vaccine ◽  
Neutralizing Antibodies ◽  
Th2 Response ◽  
Vaccine Trials ◽  
Lower Respiratory Tract Disease ◽  
Rsv Infection ◽  
Syncytial Virus ◽  
Tract Disease

Respiratory syncytial virus (RSV) causes severe acute lower respiratory tract disease leading to numerous hospitalizations and deaths among the infant and elderly populations worldwide. There is no vaccine or a less effective drug available against RSV infections. Natural RSV infection stimulates the Th1 immune response and activates the production of neutralizing antibodies, while earlier vaccine trials that used UV-inactivated RSV exacerbated the disease due to the activation of the allergic Th2 response. With a focus on Th1 immunity, we developed a DNA vaccine containing the native RSV fusion (RSV F) protein and studied its immune response in BALB/c mice. High levels of RSV specific antibodies were induced during subsequent immunizations. The serum antibodies were able to neutralize RSVin vitro. The RSV inhibition by sera was also shown by immunofluorescence analyses. Antibody response of the RSV F DNA vaccine showed a strong Th1 response. Also, sera from RSV F immunized and RSV infected mice reduced the RSV infection by 50% and 80%, respectively. Our data evidently showed that the RSV F DNA vaccine activated the Th1 biased immune response and led to the production of neutralizing antibodies, which is the desired immune response required for protection from RSV infections.

scholarly journals Mathematical modelling identifies the role of adaptive immunity as a key controller of respiratory syncytial virus in cotton rats

2019 ◽  
Vol 16 (160) ◽  
pp. 20190389 ◽  
Author(s):  
Darren Wethington ◽  
Olivia Harder ◽  
Karthik Uppulury ◽  
William C. L. Stewart ◽  
Phylip Chen ◽  
...  
Keyword(s):  
Immune Response ◽  
Respiratory Syncytial Virus ◽  
Mathematical Modelling ◽  
Adaptive Immune Response ◽  
Viral Titre ◽  
Adaptive Immune ◽  
Rsv Infection ◽  
Cotton Rats ◽  
Syncytial Virus

Respiratory syncytial virus (RSV) is a common virus that can have varying effects ranging from mild cold-like symptoms to mortality depending on the age and immune status of the individual. We combined mathematical modelling using ordinary differential equations (ODEs) with measurement of RSV infection kinetics in primary well-differentiated human bronchial epithelial cultures in vitro and in immunocompetent and immunosuppressed cotton rats to glean mechanistic details that underlie RSV infection kinetics in the lung. Quantitative analysis of viral titre kinetics in our mathematical model showed that the elimination of infected cells by the adaptive immune response generates unique RSV titre kinetic features including a faster timescale of viral titre clearance than viral production, and a monotonic decrease in the peak RSV titre with decreasing inoculum dose. Parameter estimation in the ODE model using a nonlinear mixed effects approach revealed a very low rate (average single-cell lifetime > 10 days) of cell lysis by RSV before the adaptive immune response is initiated. Our model predicted negligible changes in the RSV titre kinetics at early times post-infection (less than 5 dpi) but a slower decay in RSV titre in immunosuppressed cotton rats compared to that in non-suppressed cotton rats at later times (greater than 5 dpi) in silico. These predictions were in excellent agreement with the experimental results. Our combined approach quantified the importance of the adaptive immune response in suppressing RSV infection in cotton rats, which could be useful in testing RSV vaccine candidates.

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