scholarly journals Treatment with respiratory syncytial virus G glycoprotein monoclonal antibody or F(ab′)2 components mediates reduced pulmonary inflammation in mice

2009 ◽  
Vol 90 (5) ◽  
pp. 1119-1123 ◽  
Author(s):  
Congrong Miao ◽  
Gertrud U. Radu ◽  
Hayat Caidi ◽  
Ralph A. Tripp ◽  
Larry J. Anderson ◽  
...  
Keyword(s):  
Monoclonal Antibody ◽  
Respiratory Syncytial Virus ◽  
Interferon Gamma ◽  
Virus Replication ◽  
Pulmonary Inflammation ◽  
Leukocyte Trafficking ◽  
Virus Clearance ◽  
Neutralizing Monoclonal Antibody ◽  
Rsv Infection ◽  
Syncytial Virus

Therapeutic treatment with a non-neutralizing monoclonal antibody (mAb) (131-2G) specific to respiratory syncytial virus (RSV) G glycoprotein mediates virus clearance and decreases leukocyte trafficking and interferon gamma (IFN-γ) production in the lungs of RSV-infected mice. Its F(ab′)2 component only mediates decreased leukocyte trafficking and IFN-γ production without reducing virus replication. Thus, this mAb has two independent actions that could facilitate treatment and/or prevention of RSV infection by reducing both virus replication and virus-induced pulmonary inflammation.

scholarly journals Prophylactic Administration of a Complementarity-Determining Region Derived from a Neutralizing Monoclonal Antibody Is Effective against Respiratory Syncytial Virus Infection in BALB/c Mice

1998 ◽  
Vol 72 (1) ◽  
pp. 807-810 ◽  
Author(s):  
C. Bourgeois ◽  
J. B. Bour ◽  
L. S. Aho ◽  
P. Pothier
Keyword(s):  
Monoclonal Antibody ◽  
Monoclonal Antibodies ◽  
Respiratory Syncytial Virus ◽  
Lung Infection ◽  
Neutralizing Monoclonal Antibody ◽  
Rsv Infection ◽  
Syncytial Virus ◽  
Complementarity Determining Region ◽  
Single Peptide

ABSTRACT Immunotherapy with antibodies against respiratory syncytial virus (RSV) is a treatment option given the absence of any vaccine or other available satisfactory treatment. We selected one of our monoclonal antibodies, RS-348, that is highly neutralizing. We showed that a single peptide (PEP3H) derived from complementarity-determining region 3 (CDR3) of its heavy chain was capable of neutralizing the virusin vitro. When intranasally administered 24 h before challenge, this peptide protected BALB/c mice against RSV lung infection. These results indicate that a single CDR can be effective against RSV infection.

scholarly journals Prophylactic Treatment with a G Glycoprotein Monoclonal Antibody Reduces Pulmonary Inflammation in Respiratory Syncytial Virus (RSV)-Challenged Naïve and Formalin-Inactivated RSV-Immunized BALB/c Mice

2010 ◽  
Vol 84 (18) ◽  
pp. 9632-9636 ◽  
Author(s):  
Gertrud U. Radu ◽  
Hayat Caidi ◽  
Congrong Miao ◽  
Ralph A. Tripp ◽  
Larry J. Anderson ◽  
...  
Keyword(s):  
Monoclonal Antibody ◽  
Respiratory Syncytial Virus ◽  
Inflammatory Response ◽  
G Protein ◽  
Primary Infection ◽  
Prophylactic Treatment ◽  
Pulmonary Inflammation ◽  
Rsv Infection ◽  
Pulmonary Inflammatory Response ◽  
Syncytial Virus

ABSTRACT We examined whether prophylactically administered anti-respiratory syncytial virus (anti-RSV) G monoclonal antibody (MAb) would decrease the pulmonary inflammation associated with primary RSV infection and formalin-inactivated RSV (FI-RSV)-enhanced disease in mice. MAb 131-2G administration 1 day prior to primary infection reduced the pulmonary inflammatory response and the level of RSV replication. Further, intact or F(ab′)2 forms of MAb 131-2G administered 1 day prior to infection in FI-RSV-vaccinated mice reduced enhanced inflammation and disease. This study shows that an anti-RSV G protein MAb might provide prophylaxis against both primary infection and FI-RSV-associated enhanced disease. It is possible that antibodies with similar reactivities might prevent enhanced disease and improve the safety of nonlive virus vaccines.

scholarly journals Eosinophils contribute to innate antiviral immunity and promote clearance of respiratory syncytial virus

Blood ◽  
2007 ◽  
Vol 110 (5) ◽  
pp. 1578-1586 ◽  
Author(s):  
Simon Phipps ◽  
Chuan En Lam ◽  
Suresh Mahalingam ◽  
Matthew Newhouse ◽  
Ruben Ramirez ◽  
...  
Keyword(s):  
Respiratory Syncytial Virus ◽  
Host Defense ◽  
No Production ◽  
Wild Type ◽  
Interleukin 5 ◽  
Virus Clearance ◽  
Lung Dysfunction ◽  
Rsv Infection ◽  
Syncytial Virus

AbstractEosinophils are recruited to the lungs in response to respiratory syncytial virus (RSV) infection; however, their role in promoting antiviral host defense remains unclear. Here, we demonstrate that eosinophils express TLRs that recognize viral nucleic acids, are activated and degranulate after single-stranded RNA (ssRNA) stimulation of the TLR-7–MyD88 pathway, and provide host defense against RSV that is MyD88 dependent. In contrast to wild-type mice, virus clearance from lung tissue was more rapid in hypereosinophilic (interleukin-5 transgenic) mice. Transfer of wild-type but not MyD88-deficient eosinophils to the lungs of RSV-infected wild-type mice accelerated virus clearance and inhibited the development of airways hyperreactivity. Similar responses were observed when infected recipient mice were MyD88 deficient. Eosinophils isolated from infected hypereosinophilic MyD88-sufficient but not MyD88-deficient mice expressed greater amounts of IFN regulatory factor (IRF)–7 and eosinophil-associated ribonucleases EAR-1 and EAR-2. Hypereosinophilia in the airways of infected mice also correlated with increased expression of IRF-7, IFN-β, and NOS-2, and inhibition of NO production with the NOS-2 inhibitor L-NMA partially reversed the accelerated virus clearance promoted by eosinophils. Collectively, our results demonstrate that eosinophils can protect against RSV in vivo, as they promote virus clearance and may thus limit virus-induced lung dysfunction.

scholarly journals The Role of Toll-like receptor 4 in respiratory syncytial virus replication, interferon lambda 1 induction, and chemokine responses

2018 ◽  
Author(s):  
Lindsay Broadbent ◽  
Jonathon D. Coey ◽  
Michael D. Shields ◽  
Ultan F. Power
Keyword(s):  
Respiratory Syncytial Virus ◽  
Immune Responses ◽  
P38 Mapk ◽  
Inflammatory Cytokines ◽  
Virus Replication ◽  
Growth Kinetics ◽  
Rsv Infection ◽  
Syncytial Virus ◽  
Pro Inflammatory Cytokines

AbstractRespiratory syncytial virus (RSV) infection is the leading cause of severe lower respiratory tract infections (LRTI) in infants worldwide. The immune responses to RSV infection are implicated in RSV pathogenesis but RSV immunopathogenesis in humans remains poorly understood. We previously demonstrated that IFN-λ1 is the principle interferon induced following RSV infection of infants and well-differentiated primary pediatric bronchial epithelial cells (WD-PBECs). Interestingly, RSV F interacts with the TLR4/CD14/MD2 complex to initiate secretion of pro-inflammatory cytokines, while TLR4 stimulation with house dust mite induces IFN-λ1 production. However, the role of TLR4 in RSV infection and concomitant IFN-λ1 induction remains unclear. Using our RSV/WD-PBEC infection model, we found that CLI-095 inhibition of TLR4 resulted in significantly reduced viral growth kinetics, and secretion of IFN-λ1 and pro-inflammatory chemokines. To elucidate specific TLR4 signalling intermediates implicated in virus replication and innate immune responses we selected 4 inhibitors, including LY294002, U0126, SB203580 and JSH-23. SB203580, a p38 MAPK inhibitor, reduced both viral growth kinetics and IFN-λ1 secretion, while JSH-23, an NF-κB inhibitor, reduced IFN-λ1 secretion without affecting virus growth kinetics. Our data indicate that TLR4 plays a role in RSV entry and/or replication and IFN-λ1 induction following RSV infection is mediated, in part, by TLR4 signalling through NF- κB and/or p38 MAPK. Therefore, targeting TLR4 or downstream effector proteins could present novel treatment strategies against RSV.ImportanceThe role of TLR4 in RSV infection and IFN-λ1 induction is controversial. Using our WD-PBEC model, which replicates many hallmarks of RSV infection in vivo, we demonstrated that the TLR4 pathway is involved in both RSV infection and/or replication and the concomitant induction of IFN-λ1 and other pro-inflammatory cytokines. Increasing our understanding of the role of TLR4 in RSV immunopathogenesis may lead to the development of novel RSV therapeutics.

scholarly journals Monoclonal Antibody against G Glycoprotein Increases Respiratory Syncytial Virus Clearance In Vivo and Prevents Vaccine-Enhanced Diseases

PLoS ONE ◽  
2017 ◽  
Vol 12 (1) ◽  
pp. e0169139 ◽  
Author(s):  
Hyo-Jeong Lee ◽  
Jeong-Yoon Lee ◽  
Min-Hee Park ◽  
Joo-Young Kim ◽  
Jun Chang
Keyword(s):  
Monoclonal Antibody ◽  
Respiratory Syncytial Virus ◽  
Virus Clearance ◽  
Syncytial Virus

scholarly journals Respiratory syncytial virus infection: an innate perspective

F1000Research ◽  
2016 ◽  
Vol 5 ◽  
pp. 2898 ◽  
Author(s):  
Cecilia Johansson
Keyword(s):  
Respiratory Syncytial Virus ◽  
Severe Disease ◽  
Upper Respiratory Tract ◽  
Term Infants ◽  
Virus Clearance ◽  
Adaptive Immune Cells ◽  
Immune Mediated ◽  
Rsv Infection ◽  
Syncytial Virus ◽  
Lower Respiratory Disease

Respiratory syncytial virus (RSV) is a common cause of upper respiratory tract infection in children and adults. However, infection with this virus sometimes leads to severe lower respiratory disease and is the major cause of infant hospitalisations in the developed world. Several risk factors such as baby prematurity and congenital heart disease are known to predispose towards severe disease but previously healthy, full-term infants can also develop bronchiolitis and viral pneumonia during RSV infection. The causes of severe disease are not fully understood but may include dysregulation of the immune response to the virus, resulting in excessive recruitment and activation of innate and adaptive immune cells that can cause damage. This review highlights recent discoveries on the balancing act of immune-mediated virus clearance versus immunopathology during RSV infection.

scholarly journals Pneumoviruses infect eosinophils and elicit MyD88-dependent release of chemoattractant cytokines and interleukin-6

Blood ◽  
2009 ◽  
Vol 114 (13) ◽  
pp. 2649-2656 ◽  
Author(s):  
Kimberly D. Dyer ◽  
Caroline M. Percopo ◽  
Elizabeth R. Fischer ◽  
Stanislaw J. Gabryszewski ◽  
Helene F. Rosenberg
Keyword(s):  
Bone Marrow ◽  
Respiratory Syncytial Virus ◽  
Virus Infection ◽  
Virus Replication ◽  
Interleukin 6 ◽  
Feedback Circuit ◽  
Proinflammatory Mediators ◽  
Virus Clearance ◽  
Syncytial Virus ◽  
Human And Mouse

AbstractEosinophils are recruited to the lung in response to infection with pneumovirus pathogens and have been associated with both the pathophysiologic sequelae of infection and, more recently, with accelerated virus clearance. Here, we demonstrate that the pneumovirus pathogens, respiratory syncytial virus (RSV) and pneumonia virus of mice (PVM), can infect human and mouse eosinophils, respectively, and that virus infection of eosinophils elicits the release of disease-related proinflammatory mediators from eosinophils. RSV replication in human eosinophils results in the release of infectious virions and in the release of the proinflammatory mediator, interleukin-6 (IL-6). PVM replication in cultured bone marrow eosinophils (bmEos) likewise results in release of infectious virions and the proinflammatory mediators IL-6, IP-10, CCL2, and CCL3. In contrast to the findings reported in lung tissue of RSV-challenged mice, PVM replication is accelerated in MyD88 gene-deleted bmEos, whereas release of cytokines is diminished. Interestingly, exogenous IL-6 suppresses virus replication in MyD88 gene-deleted bmEos, suggesting a role for a MyD88-dependent cytokine-mediated feedback circuit in modulating this response. Taken together, our findings suggest that eosinophils are targets of virus infection and may have varied and complex contributions to the pathogenesis and resolution of pneumovirus disease.

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