scholarly journals Binding and Neutralizing Capacity of Respiratory Syncytial Virus (RSV)-Specific Recombinant IgG Against RSV in Human Milk, Gastric and Intestinal Fluids from Infants

Nutrients ◽  
2020 ◽  
Vol 12 (7) ◽  
pp. 1904 ◽  
Author(s):  
Veronique Demers-Mathieu ◽  
Jiraporn Lueangsakulthai ◽  
Yunyao Qu ◽  
Brian P. Scottoline ◽  
David C. Dallas
Keyword(s):  
Flow Cytometry ◽  
Respiratory Syncytial Virus ◽  
Human Milk ◽  
Binding Capacity ◽  
Recombinant Antibody ◽  
Viral Pathogen ◽  
Neutralizing Capacity ◽  
Gastric Contents ◽  
Syncytial Virus ◽  
Syncytia Formation

Oral administration of pathogen-specific recombinant antibodies may help to prevent infant gastrointestinal (GI) pathogen infection; however, to neutralize an infectious agent, these antibodies must resist degradation in the GI tract. Palivizumab, a recombinant antibody specific for the respiratory syncytial virus (RSV), was used as a model for pathogen-specific IgG in human milk. The aim was to compare the remaining binding capacity of palivizumab in milk between three mothers after exposure to an in vitro model of infant gastrointestinal digestion (gastric and duodenal fluids) using ELISA. The neutralizing capacity of palivizumab in pooled human milk, gastric contents, and stools from preterm infants was also evaluated for blocking RSV with green fluorescent protein (RSV-GFP) infection in Hep-2 cells using confocal and inverted microscopy and flow cytometry. The reduction of palivizumab binding capacity in human milk and digested samples was slightly different between mothers. Overall, palivizumab decreased 50% after simulated gastric digestion with pepsin and 62% after simulated intestinal digestion with pancreatin. Palivizumab (2–8 μg/mL) in human milk or stool samples blocked RSV (3.4 × 104 FFU/mL) infection (no syncytia formation on Hep-2 cells) by microscopy. Syncytia formation was detected on Hep-2 cells when RSV was incubated in gastric contents or virus medium with 2–4 μg/mL of palivizumab, but no infection was observed at 8 μg/mL. No fluorescence (absence of infected cells) was detected when palivizumab (100 μg/mL) was incubated in human milk or medium with RSV-GFP (1.1 × 105 FFU/mL), whereas fluorescence increased with the reduced concentration of palivizumab using flow cytometry. These results suggest that undigested and digested matrices could change the binding and neutralizing capacity of viral pathogen-specific antibodies.

Severe respiratory syncytial virus disease in preterm infants: a case of innate immaturity

Thorax ◽  
2021 ◽  
pp. thoraxjnl-2020-216291
Author(s):  
Jeremy Anderson ◽  
Lien Anh Ha Do ◽  
Danielle Wurzel ◽  
Zheng Quan Toh ◽  
Kim Mulholland ◽  
...  
Keyword(s):  
Immune System ◽  
Respiratory Syncytial Virus ◽  
Preterm Infants ◽  
Innate Immune System ◽  
Virus Disease ◽  
Innate Immune ◽  
Term Infants ◽  
Viral Pathogen ◽  
Immune Biomarkers ◽  
Syncytial Virus

Respiratory syncytial virus (RSV) is the most common viral pathogen associated with acute lower respiratory tract infection (LRTI) in children under 5 years of age. Severe RSV disease is associated with the development of chronic respiratory complications such as recurrent wheezing and asthma. A common risk factor for developing severe RSV disease is premature gestation and this is largely due to an immature innate immune system. This increases susceptibility to RSV since the innate immune system is less able to protect against pathogens at a time when adaptive immunity has not fully developed. This review focuses on comparing different aspects of innate immunity between preterm and term infants to better understand why preterm infants are more susceptible to severe RSV disease. Identifying early life innate immune biomarkers associated with the development of severe RSV disease, and understanding how these compare between preterm and term infants, remains a critically important question that would aid the development of interventions to reduce the burden of disease in this vulnerable population.

Survey of WU and KI polyomaviruses, coronaviruses, respiratory syncytial virus and parechovirus in children under 5 years of age in Tehran, Iran

2020 ◽  
Author(s):  
Fahimeh Sadat Aghamirmohammadali ◽  
Kaveh Sadeghi ◽  
Nazanin Zahra Shafiei-Jandaghi ◽  
Zahra Khoban ◽  
Talat Mokhtari-Azad ◽  
...  
Keyword(s):  
Respiratory Syncytial Virus ◽  
Respiratory Infections ◽  
Virus Detection ◽  
Respiratory Viruses ◽  
Hospitalized Children ◽  
Acute Respiratory Infections ◽  
Older Children ◽  
Viral Pathogen ◽  
Syncytial Virus ◽  
Tract Infections

Background and Objectives: Severe acute respiratory infections (SARI) remain an important cause for childhood morbid- ity worldwide. We designed a research with the objective of finding the frequency of respiratory viruses, particularly WU and KI polyomaviruses (WUPyV & KIPyV), human coronaviruses (HCoVs), human respiratory syncytial virus (HRSV) and human parechovirus (HPeV) in hospitalized children who were influenza negative. Materials and Methods: Throat swabs were collected from children younger than 5 years who have been hospitalized for SARI and screened for WUPyV, KIPyV, HCoVs, HRSV and HPeV using Real time PCR. Results: A viral pathogen was identified in 23 (11.16%) of 206 hospitalized children with SARI. The rate of virus detection was considerably greater in infants <12 months (78.2%) than in older children (21.8%). The most frequently detected vi- ruses were HCoVs with 7.76% of positive cases followed by KIPyV (2%) and WUPyV (1.5%). No HPeV and HRSV were detected in this study. Conclusion: This research shown respiratory viruses as causes of childhood acute respiratory infections, while as most of mentioned viruses usually causes mild respiratory diseases, their frequency might be higher in outpatient children. Mean- while as HRSV is really sensitive to inactivation due to environmental situations and its genome maybe degraded, then for future studies, we need to use fresh samples for HRSV detection. These findings addressed a need for more studies on viral respiratory tract infections to help public health.

scholarly journals Role of CCL11 in Eosinophilic Lung Disease during Respiratory Syncytial Virus Infection

2005 ◽  
Vol 79 (4) ◽  
pp. 2050-2057 ◽  
Author(s):  
Stephen P. Matthews ◽  
John S. Tregoning ◽  
Anthony J. Coyle ◽  
Tracy Hussell ◽  
Peter J. M. Openshaw
Keyword(s):  
Respiratory Syncytial Virus ◽  
Cytokine Production ◽  
The Elderly ◽  
Viral Pathogen ◽  
Blocking Antibody ◽  
Interleukin 5 ◽  
Lung Eosinophilia ◽  
Syncytial Virus

ABSTRACT Respiratory syncytial virus (RSV) is a major viral pathogen of infants and the elderly. Significant morbidity is caused by an overexuberant mixed lung cell infiltrate, which is thought to be driven by chemokines. One of the main chemotactic mediators responsible for the movement of eosinophils is CCL11 (eotaxin). Using a mouse model of eosinophilic bronchiolitis induced by RSV, we show here that treatment in vivo with a blocking antibody to CCL11 greatly reduces lung eosinophilia and disease severity. In addition, anti-CCL11 caused a striking inhibition of CD4-T-cell influx and shifted cytokine production away from interleukin-5 without reducing the resistance to viral replication. These results suggest that in addition to influencing eosinophil diapedesis and survival, anti-CCL11 has an action on T cells. These studies strengthen the case for anti-CCL11 treatment of Th2-driven diseases.

scholarly journals The Heptad Repeat C Domain of the Respiratory Syncytial Virus Fusion Protein Plays a Key Role in Membrane Fusion

2017 ◽  
pp. JVI.01323-17 ◽  
Author(s):  
Imogen M. Bermingham ◽  
Keith J. Chappell ◽  
Daniel Watterson ◽  
Paul R. Young
Keyword(s):  
Amino Acids ◽  
Respiratory Syncytial Virus ◽  
Membrane Fusion ◽  
Functional Characterization ◽  
Proteolytic Processing ◽  
Heptad Repeat ◽  
Alanine Scanning Mutagenesis ◽  
Viral Pathogen ◽  
F Protein ◽  
Syncytial Virus

Respiratory syncytial virus (RSV) mediates host cell entry through the fusion (F) protein, which undergoes a conformational change to facilitate the merger of viral and host lipid membrane envelopes. RSV F comprises a trimer of disulfide bonded F1and F2subunits that is present on the virion surface in a ‘metastable' pre-fusion state. This pre-fusion form is readily triggered to undergo refolding to bring two heptad repeats (HRA and HRB) into close proximity to form a six-helix bundle that stabilizes the post-fusion form and provides the free energy required for membrane fusion. This process can be triggered independently of other proteins. Here, we have performed a comprehensive analysis of a third heptad repeat region, HRC (amino acids 75-97), an amphipathic α-helix that lies at the interface of the pre-fusion F trimer and is a major structural feature of the F2subunit. We performed alanine scanning mutagenesis from Lys-75 to Met-97 and assessed all mutations in transient cell culture for expression, proteolytic processing, cell surface localization, protein conformation and membrane fusion. Functional characterization revealed a striking distribution of activity in which fusion-increasing mutations localized to one side of the helical face, while fusion-decreasing mutations clustered on the opposing face. Herein we propose a model in which HRC plays a stabilizing role within the globular head for the pre-fusion F trimer and is potentially involved in the early events of triggering, prompting fusion peptide release and transition into the post-fusion state.IMPORTANCERSV is recognized as the most important viral pathogen amongst pediatric populations worldwide, yet no vaccine or widely available therapeutic treatment is available. The F protein is critical for the viral replication process and is the major target for neutralizing antibodies. Recent years have seen the development of pre-fusion stabilized F protein based approaches to vaccine design. A detailed understanding of the specific domains and residues that contribute to protein stability and fusion function is fundamental to such efforts. Here we present a comprehensive mutagenesis based study of a region of the RSV F2subunit (amino acids 75 - 97), referred to as HRC, and propose a role for this helical region in maintaining the delicate stability of the pre-fusion form.

scholarly journals Predominant type-2 response in infants with respiratory syncytial virus (RSV) infection demonstrated by cytokine flow cytometry

2000 ◽  
Vol 121 (2) ◽  
pp. 332-338 ◽  
Author(s):  
K. Bendelja ◽  
A. Gagro ◽  
A. Baće ◽  
R. Lokar-Kolbas ◽  
V. Kršulović-Hrešić ◽  
...  
Keyword(s):  
Flow Cytometry ◽  
Respiratory Syncytial Virus ◽  
Predominant Type ◽  
Cytokine Flow Cytometry ◽  
Rsv Infection ◽  
Syncytial Virus

scholarly journals Effect of respiratory syncytial virus infection on binding ofNeisseria meningitidisandHaemophilus influenzaetype b to a human epithelial cell line (HEp-2)

1993 ◽  
Vol 110 (2) ◽  
pp. 339-347 ◽  
Author(s):  
M. W. Raza ◽  
M. M. Ogilvie ◽  
C. C. Blackwell ◽  
J. Stewart ◽  
R. A. Elton ◽  
...  
Keyword(s):  
Flow Cytometry ◽  
Respiratory Syncytial Virus ◽  
Epithelial Cell ◽  
Epithelial Cell Line ◽  
Age Group ◽  
Type B ◽  
Human Epithelial Cell ◽  
Bacterial Binding ◽  
Infected Cells ◽  
Syncytial Virus

SUMMARYIt has been suggested that individuals might be more readily colonized with bacteria that cause meningitis through enhanced binding of the bacteria to virusinfected epithelial cells. As respiratory syncytial virus (RSV) affects infants and children in the age group also susceptible to bacterial meningitis, we tested the hypothesis that infection of HEp-2 cells by RSV might enhance binding ofNeisseria meningitidisorHaemophilus influenzaetype b (Hib). Attachment of fluorescein-labelled bacteria to HEp-2 cells was measured by flow cytometry, and RSV-infected cells bound significantly more meningococci (P< 0·001) and Hib (P< 0·01) than uninfected cells. Although the isolates expressed different antigenic characteristics (3 meningococci and 5 Hib), all showed a similar pattern of binding. The results are discussed with reference to the methods used for detection of bacterial binding and to interactions that might explain the increased binding to RSV-infected cells.

Neutralizing Activity in Human Milk Fractions against Respiratory Syncytial Virus

1986 ◽  
Vol 75 (5) ◽  
pp. 696-701 ◽  
Author(s):  
A. LÆGREID ◽  
A.-B. KOLSTø OTNÆSS ◽  
I. ØRSTAVIK ◽  
K. H. CARLSEN
Keyword(s):  
Respiratory Syncytial Virus ◽  
Human Milk ◽  
Neutralizing Activity ◽  
Syncytial Virus
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