INDUCTION OF ANTI-HUMAN CCR5 ANTIBODIES BY A BOVINE HERPESVIRUS TYPE-4 BASED VECTOR

VERNA A; FRANCESCHI V; TEBALDI G; MACCHI F; MENOZZI V; LOPALCO L; CAVIRANI S; OTONELLO S; DONOFRIO G

Conferencia; SISVet - Società Italiana delle Scienze Veterinarie; 2017

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. [1] An interesting, and actively pursued, antigen in the context of HIV infection prophylaxis (and therapy) is the CCR5 co-receptor, whose blockage by specific antibodies has been shown to inhibit both viral entry and cell-to-cell transmission of the virus. [2] Building on our previous work on the BoHV-4 vector system, we have engineered and tested a replication-competent derivative of BoHV4 (BoHV-4-CMV-hCCR5ΔTK) bearing a human CCR5 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. [1] Donofrio G., Franceschi V. et al. (2009) ?Cellular targeting of engineered heterologous antigens is a determinant factor for bovine herpesvirus 4-based vaccine vector development.? Clin Vaccine Immunol. 16(11):1675-86. [2] Lederman, M. M., Penn-Nicholson, A., Cho, M. & Mosier, D. (2006). "Biology of CCR5 and its role in HIV infection and treatment." JAMA : the journal of the American Medical Association 296, 815-826.