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Research Papers:

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

Anne K. Barasa, Peng Ye, Meredith Phelps, Ganapathiram T. Arivudainambi, Timelia Tison and Javier Gordon Ogembo _

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Oncotarget. 2017; 8:34481-34497. https://doi.org/10.18632/oncotarget.15605

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Abstract

Anne K. Barasa1,3, Peng Ye1, Meredith Phelps2, Ganapathiram T. Arivudainambi2, Timelia Tison2 and Javier Gordon Ogembo1,2

1Department of Experimental Therapeutics, Beckman Research Institute of City of Hope, Duarte, CA, USA

2Department of Medicine, University of Massachusetts Medical School, Worcester, MA, USA

3Department of Human Pathology, University of Nairobi, Nairobi, Kenya

Correspondence to:

Javier Gordon Ogembo, email: jogembo@coh.org

Keywords: kaposi sarcoma-associated herpes virus, glycoproteins, virus-like particles, cancer, prophylactic vaccine

Received: September 24, 2016    Accepted: January 16, 2017    Published: February 22, 2017

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.


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