Subunit and Virus-Like Particle Vaccine Approaches for Respiratory Syncytial Virus

2013 ◽  
pp. 285-306 ◽  
Author(s):  
Trudy G. Morrison ◽  
Edward E. Walsh
Keyword(s):  
Respiratory Syncytial Virus ◽  
Virus Like Particle ◽  
Syncytial Virus

scholarly journals Baculovirus-expressed virus-like particle vaccine in combination with DNA encoding the fusion protein confers protection against respiratory syncytial virus

Vaccine ◽  
2014 ◽  
Vol 32 (44) ◽  
pp. 5866-5874 ◽  
Author(s):  
Jong Seok Lee ◽  
Young-Man Kwon ◽  
Hye Suk Hwang ◽  
Yu-Na Lee ◽  
Eun-Ju Ko ◽  
...  
Keyword(s):  
Respiratory Syncytial Virus ◽  
Fusion Protein ◽  
Dna Encoding ◽  
Virus Like Particle ◽  
Syncytial Virus

scholarly journals Novel Respiratory Syncytial Virus-Like Particle Vaccine Composed of the Postfusion and Prefusion Conformations of the F Glycoprotein

2016 ◽  
Vol 23 (6) ◽  
pp. 451-459 ◽  
Author(s):  
Velasco Cimica ◽  
Hélène Boigard ◽  
Bipin Bhatia ◽  
John T. Fallon ◽  
Alexandra Alimova ◽  
...  
Keyword(s):  
Immune Response ◽  
Respiratory Syncytial Virus ◽  
Matrix Protein ◽  
Neutralizing Antibody ◽  
The Elderly ◽  
Mouse Lung ◽  
Oil Emulsion ◽  
Cytokines And Chemokines ◽  
Virus Like Particle ◽  
Syncytial Virus

ABSTRACTRespiratory syncytial virus (RSV) is the leading cause of severe respiratory disease in infants and children and represents an important global health burden for the elderly and the immunocompromised. Despite decades of research efforts, no licensed vaccine for RSV is available. We have developed virus-like particle (VLP)-based RSV vaccines assembled with the human metapneumovirus (hMPV) matrix protein (M) as the structural scaffold and the RSV fusion glycoprotein (F) in either the postfusion or prefusion conformation as its prime surface immunogen. Vaccines were composed of postfusion F, prefusion F, or a combination of the two conformations and formulated with a squalene-based oil emulsion as adjuvant. Immunization with these VLP vaccines afforded full protection against RSV infection and prevented detectable viral replication in the mouse lung after challenge. Analyses of lung cytokines and chemokines showed that VLP vaccination mostly induced the production of gamma interferon (IFN-γ), a marker of the Th1-mediated immune response, which is predominantly required for viral protection. Conversely, immunization with a formalin-inactivated RSV (FI-RSV) vaccine induced high levels of inflammatory chemokines and cytokines of the Th2- and Th17-mediated types of immune responses, as well as severe lung inflammation and histopathology. The VLP vaccines showed restricted production of these immune mediators and did not induce severe bronchiolitis or perivascular infiltration as seen with the FI-RSV vaccine. Remarkably, analysis of the serum from immunized mice showed that the VLP vaccine formulated using a combination of postfusion and prefusion F elicited the highest level of neutralizing antibody and enhanced the Th1-mediated immune response.

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 Nanoparticle vaccines against respiratory syncytial virus

2020 ◽  
Vol 15 (11) ◽  
pp. 763-778
Author(s):  
Laura M Stephens ◽  
Steven M Varga
Keyword(s):  
Particle Size ◽  
Respiratory Syncytial Virus ◽  
Specific Antigen ◽  
The Elderly ◽  
Precise Control ◽  
Effector T Cell ◽  
Cell Responses ◽  
Virus Like Particle ◽  
Syncytial Virus ◽  
Antigen Presenting

Respiratory syncytial virus (RSV) is a leading cause of respiratory disease in infants, the elderly and immunocompromised individuals. Despite the global burden, there is no licensed vaccine for RSV. Recent advances in the use of nanoparticle technology have provided new opportunities to address some of the limitations of conventional vaccines. Precise control over particle size and surface properties enhance antigen stability and prolong antigen release. Particle size can also be modified to target specific antigen-presenting cells in order to induce specific types of effector T-cell responses. Numerous nanoparticle-based vaccines are currently being evaluated for RSV including inorganic, polymeric and virus-like particle-based formulations. Here, we review the potential advantages of using different nanoparticle formulations in a vaccine for RSV, and discuss many examples of safe, and effective vaccines currently in both preclinical and clinical stages of testing.

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.

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