induction of antihuman c–c chemokine receptor type 5 antibodies by a bovine herpesvirus type-4 based vector
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2017
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Abstract
Bovine herpesvirus 4 (BoHV-4) is a promising vector for the delivery and intracellular expression of recombinant antigens and can thus be considered as a new prototype vaccine formulation system. An interesting, and actively pursued, antigen in the context of human immunodeficiency virus (HIV) infection prophylaxis (and therapy) is the C–C chemokine receptor type 5 (CCR5) co-receptor, whose blockage by specific antibodies has been shown to inhibit both viral entry and cell-to-cell transmission of the virus. Building on our previous work on the BoHV-4 vector system, we have engineered and tested a replication-competent derivative of BoHV-4 (BoHV-4-CMV-hCCR5ΔTK) bearing a human CCR5 (hCCR5) expression cassette. We show here that CCR5 is indeed expressed at high levels in multiple types of BoHV-4-CMV-hCCR5ΔTK-infected cells. More importantly, two intravenous inoculations of CCR5-expressing BoHV-4 virions into rabbits led to the production of anti-CCR5 antibodies capable of reacting with the CCR5 receptor exposed on the surface of HEK293T cells through specific recognition of the amino-terminal region (aa 14–34) of the protein. Given the growing interest for anti-CCR5 immunization as an HIV control strategy and the many advantages of virus-based immunogen formulations (especially for poorly immunogenic or self-antigens), the results reported in this study provide preliminary validation of BoHV-4 as a safe viral vector suitable for CCR5 vaccination.
| Reference Key |
verna2017frontiersinduction
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| Authors | ;Andrea Elizabeth Verna;Valentina Franceschi;Giulia Tebaldi;Francesca Macchi;Valentina Menozzi;Claudia Pastori;Lucia Lopalco;Simone Ottonello;Sandro Cavirani;Gaetano Donofrio |
| Journal | sudebno-meditsinskaia ekspertiza |
| Year | 2017 |
| DOI |
10.3389/fimmu.2017.01402
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