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 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.

scholarly journals Differential Mucin Expression by Respiratory Syncytial Virus and Human Metapneumovirus Infection in Human Epithelial Cells

2015 ◽  
Vol 2015 ◽  
pp. 1-7 ◽  
Author(s):  
Ma. Del Rocío Baños-Lara ◽  
Boyang Piao ◽  
Antonieta Guerrero-Plata
Keyword(s):  
Immune Response ◽  
Respiratory Syncytial Virus ◽  
Epithelial Cells ◽  
Viral Infections ◽  
Human Metapneumovirus ◽  
Human Epithelial Cells ◽  
Mucin Expression ◽  
Rsv Infection ◽  
Syncytial Virus ◽  
Tract Disease

Mucins (MUC) constitute an important component of the inflammatory and innate immune response. However, the expression of these molecules by respiratory viral infections is still largely unknown. Respiratory syncytial virus (RSV) and human metapneumovirus (hMPV) are two close-related paramyxoviruses that can cause severe low respiratory tract disease in infants and young children worldwide. Currently, there is not vaccine available for neither virus. In this work, we explored the differential expression of MUC by RSV and hMPV in human epithelial cells. Our data indicate that the MUC expression by RSV and hMPV differs significantly, as we observed a stronger induction of MUC8, MUC15, MUC20, MUC21, and MUC22 by RSV infection while the expression of MUC1, MUC2, and MUC5B was dominated by the infection with hMPV. These results may contribute to the different immune response induced by these two respiratory viruses.

Ribavirin. Red Book Committee Recommendations Questioned

PEDIATRICS ◽  
1994 ◽  
Vol 93 (4) ◽  
pp. 672-673
Author(s):  
Ellen R. Wald ◽  
Barry Dashefsky
Keyword(s):  
High Risk ◽  
Lower Respiratory Tract ◽  
Respiratory Tract Disease ◽  
American Academy Of Pediatrics ◽  
Lower Respiratory Tract Disease ◽  
Rsv Infection ◽  
Syncytial Virus ◽  
Tract Disease ◽  
New Guidelines ◽  
Do So

The new guidelines provided by the Committee on Infectious Diseases of the American Academy of Pediatrics on the Use of Ribavirin in the Treatment of Respiratory Syncytial Virus Infection (RSV) are perplexing and prompt concern: "Ribavirin treatment is recommended for the following patients hospitalized with RSV lower respiratory tract disease: a. infants at high risk for severe or complicated RSV infection, including those with complicated congenital heart disease (including pulmonary hypertension); those with bronchopulmonary dysplasia, . . ."1,pp502-503 The accompanying qualifier that "the recommendations in this statement do not indicate an exclusive course of treatment or procedure to be followed"1,p501 is important but insufficient to dampen the effect of the Committee's decision to change its former stance of merely urging consideration of the use of ribavirin for patients at high risk for complications2 to an unequivocal recommendation to do so.

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.

scholarly journals Mathematical Modeling Identifies the Role of Adaptive Immunity as a Key Controller of Respiratory Syncytial Virus (RSV) Titer in Cotton Rats

2018 ◽  
Author(s):  
Darren Wethington ◽  
Olivia Harder ◽  
Karthik Uppulury ◽  
William C. L. Stewart ◽  
Phylip Chen ◽  
...  
Keyword(s):  
Immune Response ◽  
Adaptive Immune Response ◽  
Viral Titer ◽  
Vaccine Candidates ◽  
Adaptive Immune ◽  
Rsv Infection ◽  
Cotton Rats ◽  
Infected Cells ◽  
Syncytial Virus

AbstractRespiratory 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 modeling using ordinary differential equations (ODEs) with measurement of RSV infection kinetics in primary well differentiated human airway epithelial (HAE) 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 titer kinetics in our mathematical model showed that the elimination of infected cells by the adaptive immune response generates unique RSV titer kinetic features including a faster time scale of viral titer clearance than viral production, and a monotonic decrease in the peak RSV titer with decreasing inoculum dose. Parameter estimation in the ODE model using a non-linear 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 titer kinetics on earlier days (< 5 d.p.i) but a slower decay in RSV titer in immunosuppressed cotton rats compared to that in non-suppressed cotton rats at later days (>5 d.p.i) 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.ImportanceA major difficulty in developing vaccines against RSV infection is our rudimentary understanding of the mechanisms that underlie RSV infection. We addressed this challenge by developing a mechanistic computational model with predictive powers for describing RSV infection kinetics in cotton rats. The model was constructed synergistically with in vitro and in vivo measurements. The combined framework determined an important role for CD8+ T cells responses in reducing RSV titers in cotton rats. The framework can be used to design future experiments to elucidate mechanisms underlying RSV infection and test outcomes for potential vaccine candidates. In addition, estimation of the model parameters provides quantitative values for parameters of biological and clinical interest such as the replication rate of RSV, the death rate of infected cells, and the average number of new infections initiated by a single infected cell.

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 THE STUDY OF BALANCE OF Th1/Th2 IMMUNE RESPONSE DURING VIRUS-INDUCED ASTHMA EXACERBATION

2016 ◽  
Vol 13 (4-5) ◽  
pp. 20-28
Author(s):  
A R Gaisina ◽  
I P Shilovskiy ◽  
A A Nikonova ◽  
M S Sundukova ◽  
M A Zaretskaia ◽  
...  
Keyword(s):  
Immune Response ◽  
Allergic Inflammation ◽  
Current Data ◽  
Th2 Response ◽  
Common Chronic Disease ◽  
Asthma Exacerbations ◽  
Th2 Immune Response ◽  
Rsv Infection ◽  
Syncytial Virus

Bronchial asthma (BA) is the most common chronic disease of the airways affecting up to 18% of population in different regions of the world. Respiratory viruses such as rhinoviruses and respiratory syncytial virus (RSV) are the main causes of BA exacerbations. Current data demonstrate the major role of Th1- and Th2-response and corresponding cytokines in the development of infectious and allergic inflammation of the airways. At the same time, there are no data available concerning changes in Th1/Th2-balance during virus-induced asthma exacerbations. In the current study, we evaluated Th1/Th2-balance using developed mouse model of RSV-induced BA exacerbation. In was demonstrated, that RSV infection does not increase Th2-immune response but enhances Th1-response that shifts Th1/Th2-balance towards Th1.

scholarly journals Human Respiratory Syncytial Virus NS 1 Targets TRIM25 to Suppress RIG-I Ubiquitination and Subsequent RIG-I-Mediated Antiviral Signaling

Viruses ◽  
2018 ◽  
Vol 10 (12) ◽  
pp. 716 ◽  
Author(s):  
Junsu Ban ◽  
Na-Rae Lee ◽  
Noh-Jin Lee ◽  
Jong Kil Lee ◽  
Fu-Shi Quan ◽  
...  
Keyword(s):  
Respiratory Syncytial Virus ◽  
Viral Infections ◽  
Ectopic Expression ◽  
Suppressive Effect ◽  
Type I ◽  
Antiviral Signaling ◽  
Lower Respiratory Tract Disease ◽  
Rsv Infection ◽  
Syncytial Virus ◽  
Tract Disease

Respiratory syncytial virus (RSV) causes severe acute lower respiratory tract disease. Retinoic acid-inducible gene-I (RIG-I) serves as an innate immune sensor and triggers antiviral responses upon recognizing viral infections including RSV. Since tripartite motif-containing protein 25 (TRIM25)-mediated K63-polyubiquitination is crucial for RIG-I activation, several viruses target initial RIG-I activation through ubiquitination. RSV NS1 and NS2 have been shown to interfere with RIG-I-mediated antiviral signaling. In this study, we explored the possibility that NS1 suppresses RIG-I-mediated antiviral signaling by targeting TRIM25. Ubiquitination of ectopically expressed RIG-I-2Cards domain was decreased by RSV infection, indicating that RSV possesses ability to inhibit TRIM25-mediated RIG-I ubiquitination. Similarly, ectopic expression of NS1 sufficiently suppressed TRIM25-mediated RIG-I ubiquitination. Furthermore, interaction between NS1 and TRIM25 was detected by a co-immunoprecipitation assay. Further biochemical assays showed that the SPRY domain of TRIM25, which is responsible for interaction with RIG-I, interacted sufficiently with NS1. Suppression of RIG-I ubiquitination by NS1 resulted in decreased interaction between RIG-I and its downstream molecule, MAVS. The suppressive effect of NS1 on RIG-I signaling could be abrogated by overexpression of TRIM25. Collectively, this study suggests that RSV NS1 interacts with TRIM25 and interferes with RIG-I ubiquitination to suppress type-I interferon signaling.

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.

scholarly journals Mathematical Modeling Identifies the Role of Adaptive Immunity as a Key Controller of Respiratory Syncytial Virus (RSV) Titer in Cotton Rats

2018 ◽  
Author(s):  
Darren Wethington ◽  
Olivia Harder ◽  
Karthik Uppulury ◽  
William C. L. Stewart ◽  
Phylip Chen ◽  
...  
Keyword(s):  
Immune Response ◽  
Adaptive Immune Response ◽  
Viral Titer ◽  
Vaccine Candidates ◽  
Adaptive Immune ◽  
Rsv Infection ◽  
Cotton Rats ◽  
Infected Cells ◽  
Syncytial Virus

AbstractRespiratory 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 modeling using ordinary differential equations (ODEs) with measurement of RSV infection kinetics in primary well differentiated human airway epithelial (HAE) 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 titer kinetics in our mathematical model showed that the elimination of infected cells by the adaptive immune response generates unique RSV titer kinetic features including a faster time scale of viral titer clearance than viral production, and a monotonic decrease in the peak RSV titer with decreasing inoculum dose. Parameter estimation in the ODE model using a non-linear 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 titer kinetics on earlier days (< 5 d.p.i) but a slower decay in RSV titer at later days (>5 d.p.i) in immunosuppressed cotton rats compared to that in non-suppressed cotton rats 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.ImportanceA major difficulty in developing vaccines against RSV infection is our rudimentary understanding of the mechanisms that underlie RSV infection. We addressed this challenge by developing a mechanistic computational model with predictive powers for describing RSV infection kinetics in cotton rats. The model was constructed synergistically with in vitro and in vivo measurements. The combined framework determined an important role for CD8+ T cells responses in reducing RSV titers in cotton rats. The framework can be used to design future experiments to elucidate mechanisms underlying RSV infection and test outcomes for potential vaccine candidates. In addition, estimation of the model parameters provides quantitative values for parameters of biological and clinical interest such as the replication rate of RSV, the death rate of infected cells, and the average number of new infections initiated by a single infected cell.

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