title: Bovine herpesvirus 4-based vector delivering a hybrid rat/human HER-2 oncoantigen efficiently protects mice from autochthonous Her-2+mammary cancer.
abstract: The epidermal growth factor receptor 2 (HER-2) oncogene is a major target for the immunotherapy of breast cancer. Following up to the therapeutic success achieved with Her-2-targeting monoclonal antibodies, immune-prophylactic approaches directed against Her-2 have also been investigated taking into account, and trying to overcome, Her-2 self-tolerance. Perhaps due to safety (and efficacy) concerns, the least explored anti-Her-2 active immunization strategy so far has been the one relying on viral-vectored vaccine formulations. Taking advantage of the favorable properties of bovine herpesvirus 4 (BoHV-4) in terms of safety and ease of manipulation as well as its previously documented ability to transduce and confer immunogenicity to heterologous antigens, we tested the ability of different recombinant HER-2-BoHV-4 immunogens to 8break tolerance and elicit a protective, anti-mammary tumor antibody response in HER-2 transgenic BALB-neuT mice. All the tested constructs expressed the HER-2 transgenes at high levels and elicited significant cellular immune responses in BALB/c mice upon administration via either DNA vaccination or viral infection. In BALB-neuT mice, instead, only the viral construct expressing the membrane-bound chimeric form of Her-2 protein (BoHV-4-RHuT-gD) elicited a humoral immune response that was more intense and earlier-appearing than that induced by DNA vaccination. In keeping with this observation, two administrations of BoHV-4-RHuT-gD effectively protected BALB-neuT mice from tumor formation, with 50% of vaccinated animals tumor-free after 30 weeks from immunization compared to 100% of animals exhibiting at least one palpable tumor in the case of animals vaccinated with the other BoHV-4-HER-2 constructs.
authors.affiliation: Department of Medical-Veterinary Science, University of Parma , Parma, Italy.
authors.forename: Sarah
authors.initials: S
authors.lastname: Jacca
authors.affiliation: Department of Molecular Biotechnology and Health Sciences, Molecular Biotechnology Center, University of Torino , Torino, Italy.
authors.forename: Valeria
authors.initials: V
authors.lastname: Rolih
authors.affiliation: Department of Molecular Biotechnology and Health Sciences, Molecular Biotechnology Center, University of Torino , Torino, Italy.
authors.forename: Elena
authors.initials: E
authors.lastname: Quaglino
authors.affiliation: Department of Medical-Veterinary Science, University of Parma , Parma, Italy.
authors.forename: Valentina
authors.initials: V
authors.lastname: Franceschi
authors.affiliation: Department of Medical-Veterinary Science, University of Parma , Parma, Italy.
authors.forename: Giulia
authors.initials: G
authors.lastname: Tebaldi
authors.affiliation: Department of Molecular Biotechnology and Health Sciences, Molecular Biotechnology Center, University of Torino , Torino, Italy.
authors.forename: Elisabetta
authors.initials: E
authors.lastname: Bolli
authors.affiliation: Department of Medical-Veterinary Science, University of Parma , Parma, Italy.
authors.forename: Alfonso
authors.initials: A
authors.lastname: Rosamilia
authors.affiliation: Department of Life Sciences, Biochemistry and Molecular Biology Unit, University of Parma , Parma, Italy.
authors.forename: Simone
authors.initials: S
authors.lastname: Ottonello
authors.affiliation: Department of Molecular Biotechnology and Health Sciences, Molecular Biotechnology Center, University of Torino , Torino, Italy.
authors.forename: Federica
authors.initials: F
authors.lastname: Cavallo
authors.affiliation: Department of Medical-Veterinary Science, University of Parma , Parma, Italy.
authors.forename: Gaetano
authors.initials: G
authors.lastname: Donofrio
keywords: BALB-neuT mice; BoHV-4-based vector; HER-2 antibodies; Her-2 oncogene; recombinant BoHV-4s; vaccination