title: BALB/c mice immunized with a combination of virus-like particles incorporating Kaposi sarcoma-associated herpesvirus (KSHV) envelope glycoproteins gpK8.1, gB, and gH/gL induced comparable serum neutralizing antibody activity to UV-inactivated KSHV.
abstract: Infection with Kaposi sarcoma-associated herpesvirus (KSHV) is estimated to account for over 44,000 new cases of Kaposi sarcoma annually, with 84% occurring in Africa, where the virus is endemic. To date, there is no prophylactic vaccine against KSHV. KSHV gpK8.1, gB, and gH/gL glycoproteins, implicated in the virus entry into host cells, are attractive vaccine targets for eliciting potent neutralizing antibodies (nAbs) against virus infection. We incorporated gpK8.1, gB, or gH/gL on the surface of virus-like particles (VLPs) and characterized these VLPs for their composition, size, and functionality. To determine which viral glycoprotein(s) elicit the most effective serum-nAbs, we immunized BALB/c mice with gpK8.1, gB, or gH/gL VLPs individually or in combination. Neutralizing antibody assay revealed that sera from mice immunized with the VLPs inhibited KSHV infection of HEK-293 cells in a dose-dependent manner. As a single immunogen, gpK8.1 VLPs stimulated comparable nAb activity to that of UV-inactivated KSHV (UV-KSHV). In contrast, UV-KSHV stimulated higher titers of nAb compared to gB (p = 0.0316) or gH/gL (p = 0.0486). Mice immunized with the combination of gB and gH/gL VLPs had a better nAb response than those immunized with either gB (p = 0.0268), or gH/gL (p = 0.0397) as single VLP immunogens. Immunization with any VLP combination stimulated comparable nAb activity to UV-KSHV serum. Our data provide the first evidence that KSHV gpK8.1, gB, and gH/gL glycoproteins can be incorporated onto the surface of VLPs and used as prophylactic vaccine candidates, with potential to prevent KSHV infection.
authors.affiliation: Department of Experimental Therapeutics, Beckman Research Institute of City of Hope, Duarte, CA, USA.|Department of Human Pathology, University of Nairobi, Nairobi, Kenya.
authors.forename: Anne K
authors.initials: AK
authors.lastname: Barasa
authors.affiliation: Department of Experimental Therapeutics, Beckman Research Institute of City of Hope, Duarte, CA, USA.
authors.forename: Peng
authors.initials: P
authors.lastname: Ye
authors.affiliation: Department of Medicine, University of Massachusetts Medical School, Worcester, MA, USA.
authors.forename: Meredith
authors.initials: M
authors.lastname: Phelps
authors.affiliation: Department of Medicine, University of Massachusetts Medical School, Worcester, MA, USA.
authors.forename: Ganapathiram T
authors.initials: GT
authors.lastname: Arivudainambi
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 Experimental Therapeutics, Beckman Research Institute of City of Hope, Duarte, CA, USA.|Department of Medicine, University of Massachusetts Medical School, Worcester, MA, USA.
authors.forename: Javier Gordon
authors.initials: JG
authors.lastname: Ogembo
mesh_terms: D000818:Animals; D057134:Antibodies, Neutralizing / Q000378:metabolism; D016466:CHO Cells; D019496:Cancer Vaccines / Q000008:administration & dosage* / Q000276:immunology; D002460:Cell Line; D003412:Cricetulus; D004195:Disease Models, Animal; D004305:Dose-Response Relationship, Drug; D057809:HEK293 Cells; D019288:Herpesvirus 8, Human / Q000276:immunology; D006801:Humans; D051379:Mice; D008807:Mice, Inbred BALB C; D012514:Sarcoma, Kaposi / Q000188:drug therapy* / Q000276:immunology* / Q000821:virology; D015164:Vaccines, Inactivated; D058425:Vaccines, Virus-Like Particle / Q000008:administration & dosage* / Q000276:immunology; D014759:Viral Envelope Proteins / Q000008:administration & dosage* / Q000276:immunology
chemical_list: D057134:Antibodies, Neutralizing; D019496:Cancer Vaccines; D015164:Vaccines, Inactivated; D058425:Vaccines, Virus-Like Particle; D014759:Viral Envelope Proteins
keywords: Kaposi sarcoma-associated herpes virus; cancer; glycoproteins; prophylactic vaccine; virus-like particles