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1.
Vaccine ; 39(35): 4988-5001, 2021 08 16.
Article in English | MEDLINE | ID: mdl-34304928

ABSTRACT

We evaluated enveloped virus-like particles (eVLPs) expressing various forms of the Severe acute respiratory syndrome coronavirus-2 (SARS-CoV-2) spike protein and several adjuvants in an effort to identify a highly potent Coronavirus disease 2019 (COVID-19) vaccine candidate. eVLPs expressing a modified prefusion form of SARS-CoV-2 spike protein were selected as they induced high antibody binding titers and neutralizing activity after a single injection in mice. Formulation of SARS-CoV-2 S eVLPs with aluminum phosphate resulted in balanced induction of IgG2 and IgG1 isotypes and antibody binding and neutralization titers were undiminished for more than 3 months after a single immunization. A single dose of this candidate, named VBI-2902a, protected Syrian golden hamsters from challenge with SARS-CoV-2 and supports the on-going clinical evaluation of VBI-2902a as a highly potent vaccine against COVID-19.


Subject(s)
COVID-19 , Vaccines, Virus-Like Particle , Animals , Antibodies, Neutralizing , Antibodies, Viral , COVID-19 Vaccines , Cricetinae , Humans , Mice , SARS-CoV-2 , Spike Glycoprotein, Coronavirus/genetics
2.
Clin Vaccine Immunol ; 21(2): 174-80, 2014 Feb.
Article in English | MEDLINE | ID: mdl-24334684

ABSTRACT

A prophylactic vaccine to prevent the congenital transmission of human cytomegalovirus (HCMV) in newborns and to reduce life-threatening disease in immunosuppressed recipients of HCMV-infected solid organ transplants is highly desirable. Neutralizing antibodies against HCMV confer significant protection against infection, and glycoprotein B (gB) is a major target of such neutralizing antibodies. However, one shortcoming of past HCMV vaccines may have been their failure to induce high-titer persistent neutralizing antibody responses that prevent the infection of epithelial cells. We used enveloped virus-like particles (eVLPs), in which particles were produced in cells after the expression of murine leukemia virus (MLV) viral matrix protein Gag, to express either full-length CMV gB (gB eVLPs) or the full extracellular domain of CMV gB fused with the transmembrane and cytoplasmic domains from vesicular stomatitis virus (VSV)-G protein (gB-G eVLPs). gB-G-expressing eVLPs induced potent neutralizing antibodies in mice with a much greater propensity toward epithelial cell-neutralizing activity than that induced with soluble recombinant gB protein. An analysis of gB antibody binding titers and T-helper cell responses demonstrated that high neutralizing antibody titers were not simply due to enhanced immunogenicity of the gB-G eVLPs. The cells transiently transfected with gB-G but not gB plasmid formed syncytia, consistent with a prefusion gB conformation like those of infected cells and viral particles. Two of the five gB-G eVLP-induced monoclonal antibodies we examined in detail had neutralizing activities, one of which possessed particularly potent epithelial cell-neutralizing activity. These data differentiate gB-G eVLPs from gB antigens used in the past and support their use in a CMV vaccine candidate with improved neutralizing activity against epithelial cell infection.


Subject(s)
Antibodies, Neutralizing/blood , Antibodies, Viral/blood , Cytomegalovirus Infections/prevention & control , Cytomegalovirus Vaccines/immunology , Vaccines, Virus-Like Particle/immunology , Viral Envelope Proteins/immunology , Animals , Cytomegalovirus/immunology , Cytomegalovirus Infections/immunology , Cytomegalovirus Vaccines/genetics , Cytomegalovirus Vaccines/metabolism , Epithelial Cells/virology , Female , Mice , Mice, Inbred BALB C , Vaccines, Virus-Like Particle/administration & dosage , Vaccines, Virus-Like Particle/genetics , Vaccines, Virus-Like Particle/metabolism , Viral Envelope Proteins/administration & dosage , Viral Envelope Proteins/genetics , Viral Envelope Proteins/metabolism
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