scholarly journals Newcastle Disease Virus-Like Particles Containing Respiratory Syncytial Virus G Protein Induced Protection in BALB/c Mice, with No Evidence of Immunopathology

2009 ◽  
Vol 84 (2) ◽  
pp. 1110-1123 ◽  
Author(s):  
Matthew R. Murawski ◽  
Lori W. McGinnes ◽  
Robert W. Finberg ◽  
Evelyn A. Kurt-Jones ◽  
Michael J. Massare ◽  
...  
Keyword(s):  
Respiratory Syncytial Virus ◽  
Newcastle Disease Virus ◽  
G Protein ◽  
Disease Virus ◽  
Newcastle Disease ◽  
Neutralizing Antibodies ◽  
Respiratory Infections ◽  
Chimeric Protein ◽  
Virus Like Particle ◽  
Syncytial Virus

ABSTRACT Respiratory syncytial virus (RSV) is the leading cause of serious respiratory infections in children as well as a serious cause of disease in elderly and immunosuppressed populations. There are no licensed vaccines available to prevent RSV disease. We have developed a virus-like particle (VLP) vaccine candidate for protection from RSV. The VLP is composed of the NP and M proteins of Newcastle disease virus (NDV) and a chimeric protein containing the cytoplasmic and transmembrane domains of the NDV HN protein and the ectodomain of the human RSV G protein (H/G). Immunization of mice with 10 or 40 μg total VLP-H/G protein by intraperitoneal or intramuscular inoculation stimulated antibody responses to G protein which were as good as or better than those stimulated by comparable amounts of UV-inactivated RSV. Immunization of mice with two doses or even a single dose of these particles resulted in the complete protection of mice from RSV replication in the lungs. Immunization with these particles induced neutralizing antibodies with modest titers. Upon RSV challenge of VLP-H/G-immunized mice, no enhanced pathology in the lungs was observed, although lungs of mice immunized in parallel with formalin-inactivated RSV (FI-RSV) showed the significant pathology that has previously been documented after immunization with FI-RSV. Thus, the VLP-H/G candidate vaccine was immunogenic in BALB/c mice and prevented replication of RSV in murine lungs, with no evidence of immunopathology. These data support further development of virus-like particle vaccine candidates for protection against RSV.

scholarly journals Protection against Respiratory Syncytial Virus by a Recombinant Newcastle Disease Virus Vector

2006 ◽  
Vol 80 (3) ◽  
pp. 1130-1139 ◽  
Author(s):  
Luis Martinez-Sobrido ◽  
Negin Gitiban ◽  
Ana Fernandez-Sesma ◽  
Jerome Cros ◽  
Sara E. Mertz ◽  
...  
Keyword(s):  
Respiratory Syncytial Virus ◽  
Dendritic Cell ◽  
Newcastle Disease Virus ◽  
Disease Virus ◽  
Newcastle Disease ◽  
Dendritic Cell Maturation ◽  
Cell Maturation ◽  
Viral Vaccine ◽  
Fusion Glycoprotein ◽  
Syncytial Virus

ABSTRACT Respiratory syncytial virus (RSV) is a major cause of severe lower respiratory tract disease in infants and the elderly, but no safe and effective RSV vaccine is yet available. For reasons that are not well understood, RSV is only weakly immunogenic, and reinfection occurs throughout life. This has complicated the search for an effective live attenuated viral vaccine, and past trials with inactivated virus preparations have led to enhanced immunopathology following natural infection. We have tested the hypothesis that weak stimulation of innate immunity by RSV correlates with ineffective adaptive responses by asking whether expression of the fusion glycoprotein of RSV by Newcastle disease virus (NDV) would stimulate a more robust immune response to RSV than primary RSV infection. NDV is a potent inducer of both alpha/beta interferon (IFN-α/β) production and dendritic cell maturation, while RSV is not. When a recombinant NDV expressing the RSV fusion glycoprotein was administered to BALB/c mice, they were protected from RSV challenge, and this protection correlated with a robust anti-F CD8+ T-cell response. The effectiveness of this vaccine construct reflects the differential abilities of NDV and RSV to promote dendritic cell maturation and is retained even in the absence of a functional IFN-α/β receptor.

Titration of Newcastle disease virus and its neutralizing antibodies in microplates by a modified hemadsorption and hemadsorption inhibition method

1976 ◽  
Vol 3 (3) ◽  
pp. 227-232
Author(s):  
Israel Institute for Biological Research, Ness-Ziona, Israel
Keyword(s):  
Newcastle Disease Virus ◽  
Disease Virus ◽  
Newcastle Disease ◽  
Chicken Embryo ◽  
Neutralizing Antibodies ◽  
Inhibition Test ◽  
Virus Infectivity ◽  
Embryo Fibroblasts ◽  
Microneutralization Test ◽  
Chicken Embryo Fibroblasts

Using the microtiter system, titration of Newcastle disease virus infectivity and neutralizing antibodies was carried out in chicken embryo fibroblasts grown in "U" or flat-bottomed plates. Infectivity was detected by a combined hemadsorption-hemagglutination method. Inhibition of that reaction indicated the presence of neutralizing antibodies. A 24-h microneutralization test was developed and compared to the plaque neutralization and microhemagglutination inhibition test. Reproducibility of the microneutralization test was statistically analyzed.

scholarly journals Nonglycosylated G-Protein Vaccine Protects against Homologous and Heterologous Respiratory Syncytial Virus (RSV) Challenge, while Glycosylated G Enhances RSV Lung Pathology and Cytokine Levels

2015 ◽  
Vol 89 (16) ◽  
pp. 8193-8205 ◽  
Author(s):  
Sandra Fuentes ◽  
Elizabeth M. Coyle ◽  
Hana Golding ◽  
Surender Khurana
Keyword(s):  
Respiratory Syncytial Virus ◽  
G Protein ◽  
Mammalian Cells ◽  
Neutralizing Antibodies ◽  
Protective Immunity ◽  
Protective Efficacy ◽  
Lung Pathology ◽  
Content Type ◽  
Viral Loads ◽  
Syncytial Virus

ABSTRACTNew efforts are under way to develop a vaccine against respiratory syncytial virus (RSV) that will provide protective immunity without the potential for vaccine-associated disease enhancement such as that observed in infants following vaccination with formalin-inactivated RSV vaccine. In addition to the F fusion protein, the G attachment surface protein is a target for neutralizing antibodies and thus represents an important vaccine candidate. However, glycosylated G protein expressed in mammalian cells has been shown to induce pulmonary eosinophilia upon RSV infection in a mouse model. In the current study, we evaluated in parallel the safety and protective efficacy of the RSV A2 recombinant unglycosylated G protein ectodomain (amino acids 67 to 298) expressed inEscherichia coli(REG) and those of glycosylated G produced in mammalian cells (RMG) in a mouse RSV challenge model. Vaccination with REG generated neutralizing antibodies against RSV A2 in 7/11 BALB/c mice, while RMG did not elicit neutralizing antibodies. Total serum binding antibodies against the recombinant proteins (both REG and RMG) were measured by surface plasmon resonance (SPR) and were found to be >10-fold higher for REG- than for RMG-vaccinated animals. Reduction of lung viral loads to undetectable levels after homologous (RSV-A2) and heterologous (RSV-B1) viral challenge was observed in 7/8 animals vaccinated with REG but not in RMG-vaccinated animals. Furthermore, enhanced lung pathology and elevated Th2 cytokines/chemokines were observed exclusively in animals vaccinated with RMG (but not in those vaccinated with REG or phosphate-buffered saline [PBS]) after homologous or heterologous RSV challenge. This study suggests that bacterially produced unglycosylated G protein could be developed alone or as a component of a protective vaccine against RSV disease.IMPORTANCENew efforts are under way to develop vaccines against RSV that will provide protective immunity without the potential for disease enhancement. The G attachment protein represents an important candidate for inclusion in an effective RSV vaccine. In the current study, we evaluated the safety and protective efficacy of the RSV A2 recombinant unglycosylated G protein ectodomain produced inE. coli(REG) and those of glycosylated G produced in mammalian cells (RMG) in a mouse RSV challenge model (strains A2 and B1). The unglycosylated G generated high protective immunity and no lung pathology, even in animals that lacked anti-RSV neutralizing antibodies prior to RSV challenge. Control of viral loads correlated with antibody binding to the G protein. In contrast, the glycosylated G protein provided poor protection and enhanced lung pathology after RSV challenge. Therefore, bacterially produced unglycosylated G protein holds promise as an economical approach to a protective vaccine against RSV.

scholarly journals Protection induced by virus-like particle vaccine containing tandem repeat gene of respiratory syncytial virus G protein

PLoS ONE ◽  
2018 ◽  
Vol 13 (1) ◽  
pp. e0191277 ◽  
Author(s):  
Ah-Ra Kim ◽  
Dong-Hun Lee ◽  
Su-Hwa Lee ◽  
Ilaria Rubino ◽  
Hyo-Jick Choi ◽  
...  
Keyword(s):  
Respiratory Syncytial Virus ◽  
G Protein ◽  
Tandem Repeat ◽  
Virus Like Particle ◽  
Syncytial Virus

scholarly journals Virus-Like Particle Vaccine Containing the F Protein of Respiratory Syncytial Virus Confers Protection without Pulmonary Disease by Modulating Specific Subsets of Dendritic Cells and Effector T Cells

2015 ◽  
Vol 89 (22) ◽  
pp. 11692-11705 ◽  
Author(s):  
Ki-Hye Kim ◽  
Young-Tae Lee ◽  
Hye Suk Hwang ◽  
Young-Man Kwon ◽  
Min-Chul Kim ◽  
...  
Keyword(s):  
Weight Loss ◽  
T Cells ◽  
Dendritic Cells ◽  
Respiratory Syncytial Virus ◽  
Neutralizing Antibodies ◽  
Immune Correlates ◽  
Virus Like Particle ◽  
Tnf Α ◽  
Ifn Γ ◽  
Syncytial Virus

ABSTRACTThere is no licensed vaccine against respiratory syncytial virus (RSV) since the failure of formalin-inactivated RSV (FI-RSV) due to its vaccine-enhanced disease. We investigated immune correlates conferring protection without causing disease after intranasal immunization with virus-like particle vaccine containing the RSV fusion protein (F VLP) in comparison to FI-RSV and live RSV. Upon RSV challenge, FI-RSV immune mice showed severe weight loss, eosinophilia, and histopathology, and RSV reinfection also caused substantial RSV disease despite their viral clearance. In contrast, F VLP immune mice showed least weight loss and no sign of histopathology and eosinophilia. High levels of interleukin-4-positive (IL-4+) and tumor necrosis factor alpha-positive (TNF-α+) CD4+T cells were found in FI-RSV immune mice, whereas gamma interferon-positive (IFN-γ+) and TNF-α+CD4+T cells were predominantly detected in live RSV-infected mice. More importantly, in contrast to FI-RSV and live RSV that induced higher levels of CD11b+dendritic cells, F VLP immunization induced CD8α+and CD103+dendritic cells, as well as F-specific IFN-γ+and TNF-α+CD8+T cells. These results suggest that F VLP can induce protection without causing pulmonary RSV disease by inducing RSV neutralizing antibodies, as well as modulating specific subsets of dendritic cells and CD8 T cell immunity.IMPORTANCEIt has been a difficult challenge to develop an effective and safe vaccine against respiratory syncytial virus (RSV), a leading cause of respiratory disease. Immune correlates conferring protection but preventing vaccine-enhanced disease remain poorly understood. RSV F virus-like particle (VLP) would be an efficient vaccine platform conferring protection. Here, we investigated the protective immune correlates without causing disease after intranasal immunization with RSV F VLP in comparison to FI-RSV and live RSV. In addition to inducing RSV neutralizing antibodies responsible for clearing lung viral loads, we show that modulation of specific subsets of dendritic cells and CD8 T cells producing T helper type 1 cytokines are important immune correlates conferring protection but not causing vaccine-enhanced disease.

scholarly journals A Newcastle disease virus (NDV) expressing membrane-anchored spike as a cost-effective inactivated SARS-CoV-2 vaccine

2020 ◽  
Author(s):  
Weina Sun ◽  
Stephen McCroskery ◽  
Wen-Chun Liu ◽  
Sarah R. Leist ◽  
Yonghong Liu ◽  
...  
Keyword(s):  
Newcastle Disease Virus ◽  
Disease Virus ◽  
Newcastle Disease ◽  
Neutralizing Antibodies ◽  
Protective Efficacy ◽  
Low Cost ◽  
Production Capacity ◽  
Cost Effective ◽  
Influenza Virus Vaccine ◽  
Global Scale

A successful SARS-CoV-2 vaccine must be not only safe and protective but must also meet the demand on a global scale at low cost. Using the current influenza virus vaccine production capacity to manufacture an egg-based inactivated Newcastle disease virus (NDV)/SARS-CoV-2 vaccine would meet that challenge. Here, we report pre-clinical evaluations of an inactivated NDV chimera stably expressing the membrane-anchored form of the spike (NDV-S) as a potent COVID-19 vaccine in mice and hamsters. The inactivated NDV-S vaccine was immunogenic, inducing strong binding and/or neutralizing antibodies in both animal models. More importantly, the inactivated NDV-S vaccine protected animals from SARS-CoV-2 infections or significantly attenuated SARS-CoV-2 induced disease. In the presence of an adjuvant, antigen-sparing could be achieved, which would further reduce the cost while maintaining the protective efficacy of the vaccine.

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