Induction of Antihuman C–C Chemokine Receptor Type 5 Antibodies by a Bovine Herpesvirus Type-4 Based Vector

VERNA, ANDREA ELIZABETH; FRANCESCHI, VALENTINA; TEBALDI, GIULIA; MACCHI, FRANCESCA; MENOZZI, VALENTINA; PASTORI, CLAUDIA; LOPALCO, LUCIA; OTTONELLO, SIMONE; CAVIRANI, SANDRO; DONOFRIO, GAETANO

Frontiers in Immunology

Comparative Immunology

Lugar: Viena; Año: 2017 vol. 8

Bovine herpesvirus 4 (BoHV-4) is a promising vector for the delivery and intracellularexpression of recombinant antigens and can thus be considered as a new prototypevaccine formulation system. An interesting, and actively pursued, antigen in the contextof human immunodeficiency virus (HIV) infection prophylaxis (and therapy) is the C?Cchemokine receptor type 5 (CCR5) co-receptor, whose blockage by specific antibodieshas 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 andtested a replication-competent derivative of BoHV-4 (BoHV-4-CMV-hCCR5ΔTK) bearinga human CCR5 (hCCR5) expression cassette. We show here that CCR5 is indeedexpressed at high levels in multiple types of BoHV-4-CMV-hCCR5ΔTK-infected cells.More importantly, two intravenous inoculations of CCR5-expressing BoHV-4 virions intorabbits led to the production of anti-CCR5 antibodies capable of reacting with the CCR5receptor exposed on the surface of HEK293T cells through specific recognition of theamino-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-basedimmunogen formulations (especially for poorly immunogenic or self-antigens), the resultsreported in this study provide preliminary validation of BoHV-4 as a safe viral vectorsuitable for CCR5 vaccination.