scholarly journals Vaccination To Induce Antibodies Blocking the CX3C-CX3CR1 Interaction of Respiratory Syncytial Virus G Protein Reduces Pulmonary Inflammation and Virus Replication in Mice

2009 ◽  
Vol 84 (2) ◽  
pp. 1148-1157 ◽  
Author(s):  
Wenliang Zhang ◽  
Youngjoo Choi ◽  
Lia M. Haynes ◽  
Jennifer L. Harcourt ◽  
Larry J. Anderson ◽  
...  
Keyword(s):  
Respiratory Syncytial Virus ◽  
G Protein ◽  
Pulmonary Inflammation ◽  
Body Weight Loss ◽  
Effective Vaccine ◽  
Vaccine Strategy ◽  
Rsv Infection ◽  
Syncytial Virus ◽  
Substantial Morbidity ◽  
High Risk Children

ABSTRACT Respiratory syncytial virus (RSV) infection causes substantial morbidity and some deaths in the young and elderly worldwide. There is no safe and effective vaccine available, although it is possible to reduce the hospitalization rate for high-risk children by anti-RSV antibody prophylaxis. RSV has been shown to modify the immune response to infection, a feature linked in part to RSV G protein CX3C chemokine mimicry. This study determined if vaccination with G protein polypeptides or peptides spanning the central conserved region of the G protein could induce antibodies that blocked G protein CX3C-CX3CR1 interaction and disease pathogenesis mediated by RSV infection. The results show that mice vaccinated with G protein peptides or polypeptides containing the CX3C motif generate antibodies that inhibit G protein CX3C-CX3CR1 binding and chemotaxis, reduce lung virus titers, and prevent body weight loss and pulmonary inflammation. The results suggest that RSV vaccines that induce antibodies that block G protein CX3C-CX3CR1 interaction may offer a new, safe, and efficacious RSV vaccine strategy.

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.

DNA encoding the attachment (G) or fusion (F) protein of respiratory syncytial virus induces protection in the absence of pulmonary inflammation

2000 ◽  
Vol 81 (10) ◽  
pp. 2519-2523 ◽  
Author(s):  
Gary P. Bembridge ◽  
Nuria Rodriguez ◽  
Regina Garcia-Beato ◽  
Carolyn Nicolson ◽  
Jose A. Melero ◽  
...  
Keyword(s):  
Respiratory Syncytial Virus ◽  
Antibody Response ◽  
G Protein ◽  
Pulmonary Inflammation ◽  
Recombinant Vaccinia Virus ◽  
Dna Encoding ◽  
Th2 Response ◽  
Rsv Infection ◽  
Ifn Γ ◽  
Syncytial Virus

Significant protection against respiratory syncytial virus (RSV) infection was induced in mice vaccinated intramuscularly (i.m.) with DNA encoding the F or G protein of RSV. The amounts of IgG1 of IgG2a antibodies in mice immunized with DNA-G alone were similar. However, the antibody response in mice co-immunized with DNA-G and DNA encoding IL-4 (DNA-IL-4) was strongly biased towards IgG1. In contrast, the antibody response in mice co-immunized with DNA-G and DNA-IL-2, -IL-12 or-IFN-γ was biased towards IgG2a. Mice vaccinated with DNA-F either alone or in combination with DNA encoding cytokines developed a predominant RSV-specific IgG2a response, which was most pronounced in mice co-immunized with DNA-F and DNA-IL-12 or -IFN-γ. Vaccinated mice developed only a slightly enhanced pulmonary inflammatory response following RSV challenge. More significantly, and in contrast to mice scarified with recombinant vaccinia virus expressing the G protein, mice vaccinated i.m. with DNA-G did not develop pulmonary eosinophilia, even when the immune response was biased towards a Th2 response by co-administration of DNA-IL-4.

scholarly journals Effect of Previous Respiratory Syncytial Virus Infection on Murine Immune Responses to F and G Protein-Containing Virus-Like Particles

2019 ◽  
Vol 93 (9) ◽  
Author(s):  
Lori McGinnes Cullen ◽  
Madelyn R. Schmidt ◽  
Trudy G. Morrison
Keyword(s):  
Respiratory Syncytial Virus ◽  
G Protein ◽  
Neutralizing Antibodies ◽  
Protective Immunity ◽  
Immune Memory ◽  
Effective Vaccine ◽  
F Protein ◽  
Virus Like Particles ◽  
Rsv Infection ◽  
Syncytial Virus

ABSTRACTMost individuals are infected with respiratory syncytial virus (RSV) by age two, but infection does not result in long-term protective immunity to subsequent infections. Previous RSV infection may, however, impact responses to an RSV vaccine. The goal of these studies was to explore the effect of previous RSV infection on murine antibody responses to RSV F and G protein-containing virus-like particles (VLP), comparing responses to those resulting from VLP immunization of RSV-naive animals. These studies showed that after RSV infection, immunization with a single dose of VLPs containing a conformation-stabilized prefusion F protein stimulated high titers of neutralizing antibodies (NA), while an immunization with post-F-containing VLPs or a second RSV infection only weakly stimulated NA, even though total anti-F protein IgG antibody levels in both VLP-immunized animals were similar. Furthermore, single pre-F or post-F VLP immunization of animals previously infected (primed) with RSV resulted in total anti-F antibody titers that were 10- to 12-fold higher than titers after a VLP prime and boost of RSV-naive animals or after two consecutive RSV infections. The avidities of serum antibodies as well as numbers of splenic B cells and bone marrow cells after different immunization protocols were also assessed. The combined results show that RSV infection can quite effectively prime animals for the production of protective antibodies that can be efficiently activated by a pre-F VLP boost but not by a post-F VLP boost or a second RSV infection.IMPORTANCEHumans may experience repeated infections caused by the same serotype of respiratory syncytial virus (RSV), in contrast to infections with most other viruses, indicating that immune memory responses to RSV are defective. However, the effects of any residual but nonprotective immunity on responses to RSV vaccines are not clear. This study demonstrates that a VLP vaccine candidate containing a stabilized prefusion F protein can robustly stimulate protective immunity in animals previously infected with RSV, while a second RSV infection or a postfusion F-containing VLP cannot. This result shows that a properly constructed immunogen can be an effective vaccine in animals previously infected with RSV. The results also suggest that the defect in RSV memory is not in the induction of that memory but rather in its activation by a subsequent RSV infection.

scholarly journals Antibiotic Minocycline Prevents Respiratory Syncytial Virus Infection

Viruses ◽  
2019 ◽  
Vol 11 (8) ◽  
pp. 739 ◽  
Author(s):  
Swapnil S. Bawage ◽  
Pooja M. Tiwari ◽  
Shreekumar Pillai ◽  
Vida A. Dennis ◽  
Shree R. Singh
Keyword(s):  
Respiratory Syncytial Virus ◽  
Specific Activity ◽  
The Body ◽  
Effective Vaccine ◽  
Mortality And Morbidity ◽  
Viral Activity ◽  
Immunodeficiency Virus ◽  
Rsv Infection ◽  
Syncytial Virus ◽  
Common Respiratory Virus

Treatment drugs, besides their specific activity, often have multiple effects on the body. The undesired effect of the drug may be repurposed as therapeutics, saving significant investigative time and effort. Minocycline has anti-cancer, anti-oxidant, anti-inflammatory, and anti-apoptotic properties. Presently, minocycline is also known to show anti-viral activity against Influenza virus, Japanese encephalitis virus, Simian immunodeficiency virus, Human immunodeficiency virus and West Nile virus. Here, we investigate the effect of minocycline on Respiratory syncytial virus (RSV), a common respiratory virus that causes severe mortality and morbidity in infants, children, and older adult populations. Currently, there is no effective vaccine or treatment for RSV infection; hence, there is a critical need for alternative and effective drug choices. Our study shows that minocycline reduces the RSV-mediated cytopathic effect and prevents RSV infection. This is the first study demonstrating the anti-viral activity of minocycline against RSV.

scholarly journals Obtaining and Characterization of the Monoclonal Antibodies Against G-Protein of the Respiratory Syncytial Virus

2020 ◽  
pp. 7-14
Author(s):  
N. A. Demidova ◽  
R. R. Klimova ◽  
A. A. Kushch ◽  
E. I. Lesnova ◽  
O. V. Masalova ◽  
...  
Keyword(s):  
Monoclonal Antibodies ◽  
Respiratory Syncytial Virus ◽  
G Protein ◽  
Clinical Samples ◽  
Enzyme Linked Immunosorbent Assay ◽  
Rsv Infection ◽  
Hybridoma Technology ◽  
Infected Cells ◽  
Syncytial Virus

The aim of this study was to obtain hybridomas producing monoclonal antibodies (Mabs) to the G-protein of the respiratory syncytial virus (RSV), and to evaluate their immunological characteristics and virus-neutralizing activity.Material and methods. Mouse Mabs were obtained using hybridoma technology. The properties of Mabs were studied by enzyme-linked immunosorbent assay (ELISA), immunofluorescence staining (IF) of infected cells, as well as by biological neutralization test in vitro (NT). To identify epitopes recognized by the Mabs on G protein ELISA additivity test was used.Results. Hybridization of splenocytes with Sp2/0 myeloma cells and primary screening showed that 75 hybridomas produce antibodies interacting with purified virus, 17 of them also react with the recombinant G-protein in ELISA. In NT 4, hybridomas suppressed in vitro RSV infection by more than 50%. Cloning of these hybridomas revealed 4 monoclones producing the most active Mabs. Mab 1C11 was IgG2a, 3 others (5D4, 5G11 and 6H4) were IgM. Three IgM Mabs actively reacted with both RSV A2 and Long, and with G-protein; Mab 1C11 was less reactive with all antigens tested. All Mabs suppressed RSV infection, while Mab 5D4 supressed it almost completely (98%). IF analysis showed that all Mabs detected RSV G-protein in the cell cytoplasm, the largest number of infected cells was detected using Mab 5D4 (80%). It was shown that the isolated Mabs were directed to two non-overlapping epitopes on the RSV G-protein.Conclusion. The isolated Mabs can be used to detect RSV in clinical samples by ELISA and IF. The isolated Mabs can be used for humanized recombinant antibodies construction and for the treatment of RSV infection in future.

scholarly journals Hepatitis B Virus Core Particles Containing a Conserved Region of the G Protein Combined with Interleukin-35 Protected Mice against Respiratory Syncytial Virus Infection without Vaccine-Enhanced Immunopathology

2020 ◽  
Vol 94 (13) ◽  
Author(s):  
Jie Yang ◽  
Chen Ma ◽  
Yu Zhao ◽  
Anjing Fan ◽  
Xiufen Zou ◽  
...  
Keyword(s):  
Respiratory Syncytial Virus ◽  
Hepatitis B Virus ◽  
Hepatitis B ◽  
G Protein ◽  
Host Response ◽  
Virus Core ◽  
B Virus ◽  
Rsv Infection ◽  
Conserved Region ◽  
Syncytial Virus

ABSTRACT Respiratory syncytial virus (RSV) is the most important cause of lower respiratory tract infection in infants and young children. The vaccine-enhanced disease (VED) has greatly hindered the development of an RSV vaccine. Currently, there are no licensed vaccines for RSV. In this study, immunization of mice with hepatitis B virus core particles containing a conserved region of the G protein (HBc-tG) combined with interleukin-35 (IL-35) elicited a Th1-biased response and a high frequency of regulatory T (Treg) cells and increased the levels of IL-10, transforming growth factor β, and IL-35 production. Importantly, immunization with HBc-tG together with IL-35 protected mice against RSV infection without vaccine-enhanced immunopathology. To explore the mechanism of how IL-35 reduces lung inflammation at the gene expression level, transcription profiles were obtained from lung tissues of immunized mice after RSV infection by the Illumina sequencing technique and further analyzed by a systems biology method. In total, 2,644 differentially expressed genes (DEGs) were identified. Twelve high-influence modules (HIMs) were selected from these DEGs on the basis of the protein-protein interaction network. A detailed analysis of HIM10, involved in the immune response network, revealed that Il10 plays a key role in regulating the host response. The selected DEGs were consistently confirmed by quantitative real-time PCR (qRT-PCR). Our results demonstrate that IL-35 inhibits vaccine-enhanced immunopathology after RSV infection and has potential for development in novel therapeutic and prophylactic strategies. IMPORTANCE In the past few decades, respiratory syncytial virus (RSV) has still been a major health concern worldwide. The vaccine-enhance disease (VED) has hindered RSV vaccine development. A truncated hepatitis B virus core protein vaccine containing the conserved region (amino acids 144 to 204) of the RSV G protein (HBc-tG) had previously been shown to induce effective immune responses and confer protection against RSV infection in mice but to also lead to VED. In this study, we investigated the effect of IL-35 on the host response and immunopathology following RSV infection in vaccinated mice. Our results indicate that HBc-tG together with IL-35 elicited a balanced immune response and protected mice against RSV infection without vaccine-enhanced immunopathology. Applying a systems biology method, we identified Il10 to be the key regulator in reducing the excessive lung inflammation. Our study provides new insight into the function of IL-35 and its regulatory mechanism of VED at the network level.

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 Heparin-Like Structures on Respiratory Syncytial Virus Are Involved in Its Infectivity In Vitro

1998 ◽  
Vol 72 (9) ◽  
pp. 7221-7227 ◽  
Author(s):  
C. Bourgeois ◽  
J. B. Bour ◽  
K. Lidholt ◽  
C. Gauthray ◽  
P. Pothier
Keyword(s):  
Respiratory Syncytial Virus ◽  
Heparan Sulfate ◽  
G Protein ◽  
Enzymatic Digestion ◽  
Virus Infectivity ◽  
Rsv Infection ◽  
Infected Cells ◽  
Virus Culture ◽  
Syncytial Virus

ABSTRACT Addition of heparin to the virus culture inhibited syncytial plaque formation due to respiratory syncytial virus (RSV). Moreover, pretreatment of the virus with heparinase or an inhibitor of heparin, protamine, greatly reduced virus infectivity. Two anti-heparan sulfate antibodies stained RSV-infected cells, but not noninfected cells, by immunofluorescence. One of the antibodies was capable of neutralizing RSV infection in vitro. These results prove that heparin-like structures identified on RSV play a major role in early stages of infection. The RSV G protein is the attachment protein. Both anti-heparan sulfate antibodies specifically bound to this protein. Enzymatic digestion of polysaccharides in the G protein reduced the binding, which indicates that heparin-like structures are on the G protein. Such oligosaccharides may therefore participate in the attachment of the virus.

scholarly journals A Single-Dose Recombinant Parainfluenza Virus 5-Vectored Vaccine Expressing Respiratory Syncytial Virus (RSV) F or G Protein Protected Cotton Rats and African Green Monkeys from RSV Challenge

2017 ◽  
Vol 91 (11) ◽  
Author(s):  
Dai Wang ◽  
Shannon Phan ◽  
Daniel J. DiStefano ◽  
Michael P. Citron ◽  
Cheryl L. Callahan ◽  
...  
Keyword(s):  
Single Dose ◽  
Respiratory Syncytial Virus ◽  
G Protein ◽  
Parainfluenza Virus ◽  
Lung Pathology ◽  
Rsv Infection ◽  
Cotton Rats ◽  
Parainfluenza Virus 5 ◽  
Syncytial Virus ◽  
Green Monkeys

ABSTRACT Human respiratory syncytial virus (RSV) is a common cause of severe respiratory disease among infants, immunocompromised individuals, and the elderly. No licensed vaccine is currently available. In this study, we evaluated two parainfluenza virus 5 (PIV5)-vectored vaccines expressing RSV F (PIV5/F) or G (PIV5/G) protein in the cotton rat and African green monkey models for their replication, immunogenicity, and efficacy of protection against RSV challenge. Following a single intranasal inoculation, both animal species shed the vaccine viruses for a limited time but without noticeable clinical symptoms. In cotton rats, the vaccines elicited RSV F- or G-specific serum antibodies and conferred complete lung protection against RSV challenge at doses as low as 103 PFU. Neither vaccine produced the enhanced lung pathology observed in animals immunized with formalin-inactivated RSV. In African green monkeys, vaccine-induced serum and mucosal antibody responses were readily detected, as well. PIV5/F provided nearly complete protection against RSV infection in the upper and lower respiratory tract at a dose of 106 PFU of vaccine. At the same dose levels, PIV5/G was less efficacious. Both PIV5/F and PIV5/G were also able to boost neutralization titers in RSV-preexposed African green monkeys. Overall, our data indicated that PIV5/F is a promising RSV vaccine candidate. IMPORTANCE A safe and efficacious respiratory syncytial virus (RSV) vaccine remains elusive. We tested the recombinant parainfluenza virus 5 (PIV5) vectors expressing RSV glycoproteins for their immunogenicity and protective efficacy in cotton rats and African green monkeys, which are among the best available animal models to study RSV infection. In both species, a single dose of intranasal immunization with PIV5-vectored vaccines was able to produce systemic and local immunity and to protect animals from RSV challenge. The vaccines could also boost RSV neutralization antibody titers in African green monkeys that had been infected previously. Our data suggest that PIV5-vectored vaccines could potentially protect both the pediatric and elderly populations and support continued development of the vector platform.

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