title: Novel Epstein-Barr virus-like particles incorporating gH/gL-EBNA1 or gB-LMP2 induce high neutralizing antibody titers and EBV-specific T-cell responses in immunized mice.
abstract: Previous Epstein-Barr virus (EBV) prophylactic vaccines based on the major surface glycoprotein gp350/220 as an immunogen have failed to block viral infection in humans, suggesting a need to target other viral envelope glycoproteins. In this study, we reasoned that incorporating gH/gL or gB, critical glycoproteins for viral fusion and entry, on the surface of a virus-like particle (VLP) would be more immunogenic than gp350/220 for generating effective neutralizing antibodies to prevent viral infection of both epithelial and B cell lines. To boost the humoral response and trigger cell-mediated immunity, EBV nuclear antigen 1 (EBNA1) and latent membrane protein 2 (LMP2), intracellular latency proteins expressed in all EBV-infected cells, were also included as critical components of the polyvalent EBV VLP. gH/gL-EBNA1 and gB-LMP2 VLPs were efficiently produced in Chinese hamster ovary cells, an FDA-approved vehicle for mass-production of biologics. Immunization with gH/gL-EBNA1 and gB-LMP2 VLPs without adjuvant generated both high neutralizing antibody titers in vitro and EBV-specific T-cell responses in BALB/c mice. These data demonstrate that will be invaluable not only in preventing EBV infection, but importantly, in preventing and treating the 200,000 cases of EBV-associated cancers that occur globally every year.
authors.affiliation: Department of Medicine, University of Massachusetts Medical School, Worcester, MA, USA.
authors.forename: Elizabeth M
authors.initials: EM
authors.lastname: Perez
authors.affiliation: Department of Experimental Therapeutics, Beckman Research Institute of City of Hope, Duarte, CA, USA.
authors.forename: Joslyn
authors.initials: J
authors.lastname: Foley
authors.affiliation: Department of Medicine, University of Massachusetts Medical School, Worcester, MA, USA.
authors.forename: Timelia
authors.initials: T
authors.lastname: Tison
authors.affiliation: Department of Medicine, University of Massachusetts Medical School, Worcester, MA, USA.
authors.forename: Rute
authors.initials: R
authors.lastname: Silva
authors.affiliation: Department of Medicine, University of Massachusetts Medical School, Worcester, MA, USA.|Department of Experimental Therapeutics, Beckman Research Institute of City of Hope, Duarte, CA, USA.
authors.forename: Javier Gordon
authors.initials: JG
authors.lastname: Ogembo
mesh_terms: D000818:Animals; D057134:Antibodies, Neutralizing / Q000097:blood* / Q000276:immunology; D016466:CHO Cells; D006224:Cricetinae; D003412:Cricetulus; D020031:Epstein-Barr Virus Infections / Q000276:immunology* / Q000821:virology; D019309:Epstein-Barr Virus Nuclear Antigens / Q000276:immunology*; D005260:Female; D004854:Herpesvirus 4, Human / Q000502:physiology; D006801:Humans; D007111:Immunity, Cellular; D007114:Immunization; D051379:Mice; D008807:Mice, Inbred BALB C; D013274:Stomach Neoplasms / Q000276:immunology* / Q000517:prevention & control / Q000821:virology; D013601:T-Lymphocytes / Q000276:immunology*; D014407:Tumor Cells, Cultured; D014763:Viral Matrix Proteins / Q000276:immunology*
chemical_list: D057134:Antibodies, Neutralizing; C037662:EBV-associated membrane antigen, Epstein-Barr virus; D019309:Epstein-Barr Virus Nuclear Antigens; D014763:Viral Matrix Proteins; C417029:EBV-encoded nuclear antigen 1
keywords: Epstein-Barr virus; vaccine; viral glycoproteins; viral latency proteins; virus-like particles