title: Enveloped virus-like particle expression of human cytomegalovirus glycoprotein B antigen induces antibodies with potent and broad neutralizing activity.
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.
authors: VBI Vaccines, Cambridge, Massachusetts, USA.
authors: Marc
authors: M
authors: Kirchmeier
authors: Anne-Catherine
authors: AC
authors: Fluckiger
authors: Catalina
authors: C
authors: Soare
authors: Jasminka
authors: J
authors: Bozic
authors: Barthelemy
authors: B
authors: Ontsouka
authors: Tanvir
authors: T
authors: Ahmed
authors: Abebaw
authors: A
authors: Diress
authors: Lenore
authors: L
authors: Pereira
authors: Florian
authors: F
authors: Schödel
authors: Stanley
authors: S
authors: Plotkin
authors: Charlotte
authors: C
authors: Dalba
authors: David
authors: D
authors: Klatzmann
authors: David E
authors: DE
authors: Anderson
mesh_terms: D000818:Animals; D057134:Antibodies, Neutralizing / Q000097:blood*; D000914:Antibodies, Viral / Q000097:blood*; D003587:Cytomegalovirus / Q000276:immunology; D003586:Cytomegalovirus Infections / Q000276:immunology / Q000517:prevention & control*; D022482:Cytomegalovirus Vaccines / Q000235:genetics / Q000276:immunology* / Q000378:metabolism; D004847:Epithelial Cells / Q000821:virology; D005260:Female; D051379:Mice; D008807:Mice, Inbred BALB C; D058425:Vaccines, Virus-Like Particle / Q000008:administration & dosage / Q000235:genetics / Q000276:immunology* / Q000378:metabolism; D014759:Viral Envelope Proteins / Q000008:administration & dosage / Q000235:genetics / Q000276:immunology* / Q000378:metabolism
chemical_list: D057134:Antibodies, Neutralizing; D000914:Antibodies, Viral; D022482:Cytomegalovirus Vaccines; D058425:Vaccines, Virus-Like Particle; D014759:Viral Envelope Proteins; C040495:glycoprotein B, Simplexvirus