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Vaccines

Enveloped Virus-Like Particle Expression of Human Cytomegalovirus Glycoprotein B Antigen Induces Antibodies with Potent and Broad Neutralizing Activity

Marc Kirchmeier, Anne-Catherine Fluckiger, Catalina Soare, Jasminka Bozic, Barthelemy Ontsouka, Tanvir Ahmed, Abebaw Diress, Lenore Pereira, Florian Schödel, Stanley Plotkin, Charlotte Dalba, David Klatzmann, David E. Anderson
D. L. Burns, Editor
Marc Kirchmeier
aVBI Vaccines, Cambridge, Massachusetts, USA
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Anne-Catherine Fluckiger
bBionaria, Saint-Genis-les-Ollières, France
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Catalina Soare
aVBI Vaccines, Cambridge, Massachusetts, USA
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Jasminka Bozic
aVBI Vaccines, Cambridge, Massachusetts, USA
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Barthelemy Ontsouka
aVBI Vaccines, Cambridge, Massachusetts, USA
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Tanvir Ahmed
aVBI Vaccines, Cambridge, Massachusetts, USA
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Abebaw Diress
aVBI Vaccines, Cambridge, Massachusetts, USA
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Lenore Pereira
cUniversity of California San Francisco, San Francisco, California, USA
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Florian Schödel
dPhilimmune LLC, Philadelphia, Pennsylvania, USA
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Stanley Plotkin
eUniversity of Pennsylvania, Philadelphia, Pennsylvania, USA
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Charlotte Dalba
aVBI Vaccines, Cambridge, Massachusetts, USA
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David Klatzmann
fUPMC University, Paris, France
gCNRS, Paris, France
hINSERM, Paris, France
iHôpital Pitié-Salpêtrière, Paris, France
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David E. Anderson
aVBI Vaccines, Cambridge, Massachusetts, USA
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D. L. Burns
Roles: Editor
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DOI: 10.1128/CVI.00662-13
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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.

  • Copyright © 2014, American Society for Microbiology. All Rights Reserved.

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Enveloped Virus-Like Particle Expression of Human Cytomegalovirus Glycoprotein B Antigen Induces Antibodies with Potent and Broad Neutralizing Activity
Marc Kirchmeier, Anne-Catherine Fluckiger, Catalina Soare, Jasminka Bozic, Barthelemy Ontsouka, Tanvir Ahmed, Abebaw Diress, Lenore Pereira, Florian Schödel, Stanley Plotkin, Charlotte Dalba, David Klatzmann, David E. Anderson
Clinical and Vaccine Immunology Jan 2014, 21 (2) 174-180; DOI: 10.1128/CVI.00662-13

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Enveloped Virus-Like Particle Expression of Human Cytomegalovirus Glycoprotein B Antigen Induces Antibodies with Potent and Broad Neutralizing Activity
Marc Kirchmeier, Anne-Catherine Fluckiger, Catalina Soare, Jasminka Bozic, Barthelemy Ontsouka, Tanvir Ahmed, Abebaw Diress, Lenore Pereira, Florian Schödel, Stanley Plotkin, Charlotte Dalba, David Klatzmann, David E. Anderson
Clinical and Vaccine Immunology Jan 2014, 21 (2) 174-180; DOI: 10.1128/CVI.00662-13
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