UMMS Affiliation

Department of Medicine, Division of Infectious Diseases and Immunology

Publication Date

2017-05-23

Document Type

Article

Disciplines

Immunology of Infectious Disease | Immunoprophylaxis and Therapy | Infectious Disease | Neoplasms | Oncology | Virus Diseases

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.

Keywords

Kaposi sarcoma-associated herpes virus, cancer, glycoproteins, prophylactic vaccine, virus-like particles

Rights and Permissions

Copyright : © 2017 Barasa et al.

DOI of Published Version

10.18/632/oncotarget.15605

Source

Oncotarget. 2017 May 23;8(21):34481-34497. doi.10.18632/oncotarget.15605. Link to article on publisher's site

Journal/Book/Conference Title

Oncotarget

Related Resources

Link to Article in PubMed

PubMed ID

28404899

Creative Commons License

Creative Commons Attribution 3.0 License
This work is licensed under a Creative Commons Attribution 3.0 License.

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