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
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Date
2017Author
Barasa, Anne K.
Peng, Ye
Meredith, Phelps
Arivudainambi, Ganapathiram T.
Timelia, Tison
Ogembo, Javier G
Type
ArticleLanguage
enMetadata
Show full item recordAbstract
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 dosedependent
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.
Citation
Barasa, Anne K., et al. "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." Oncotarget 8.21 (2017): 34481-34497.Publisher
University of Nairobi
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Attribution-NonCommercial-NoDerivs 3.0 United StatesUsage Rights
http://creativecommons.org/licenses/by-nc-nd/3.0/us/Collections
- Faculty of Health Sciences (FHS) [10387]
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