Induction of antihuman C-C chemokine receptor type 5 antibodies by a bovine herpesvirus type-4 based vector

AE Verna, V Franceschi, G Tebaldi, F Macchi, V Menozzi, C Pastori, L Lopalco, S Ottonello, S Cavirani, Gaetano Donofrio

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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-hCCR5?TK) 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-hCCR5?TK-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. © 2017 Verna, Franceschi, Tebaldi, Macchi, Menozzi, Pastori, Lopalco, Ottonello, Cavirani and Donofrio.
Original languageEnglish
Article number1402
JournalFrontiers in Immunology
Volume8
Issue number52
DOIs
Publication statusPublished - 2017

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    Verna, AE., Franceschi, V., Tebaldi, G., Macchi, F., Menozzi, V., Pastori, C., Lopalco, L., Ottonello, S., Cavirani, S., & Donofrio, G. (2017). Induction of antihuman C-C chemokine receptor type 5 antibodies by a bovine herpesvirus type-4 based vector. Frontiers in Immunology, 8(52), [1402]. https://doi.org/10.3389/fimmu.2017.01402