Bovine Herpesvirus-4-Based Vector Delivering Peste des Petits Ruminants Virus Hemagglutinin ORF Induces both Neutralizing Antibodies and Cytotoxic T Cell Responses

Abstract

Peste des Petits Ruminants Virus (PPRV) is an extremely infective morbillivirus that primarily affects goats and sheep. In underdeveloped countries where livestock are the main economical resource, PPRV causes considerable economic losses. Protective live attenuated vaccines are currently available but they induce antibody responses similar to those produced in PPRV naturally infected animals. Effective vaccines able to distinguish between vaccinated and naturally infected animals are required to PPRV control and eradication programs. Hemagglutinin (H) is a highly immunogenic PPRV envelope glycoprotein displaying both hemagglutinin and neuraminidase activities, playing a crucial role in virus attachment and penetration. In this study, a recombinant Bovine Herpesvirus-4 (BoHV-4)-based vector delivering an optimized PPRV-Hemagglutinin expression cassette, BoHV-4-A-PPRV-H-ΔTK, was assessed in immunocompetent C57BL/6 mice. BoHV-4-A-PPRV-H-ΔTK-immunization elicited both cellular and humoral immune responses with specific T cell, cytotoxic T lymphocyte, and sero-neutralizing antibody against PPRV. These data suggest recombinant BoHV-4-A-PPRV-H-ΔTK as an effective vaccine candidate to protect against PPRV herd infection and potentially applicable for eradication programs.

A recombinant bovine herpesvirus-4 vectored vaccine delivered via intranasal nebulization elicits viral neutralizing antibody titers in cattle

“…In light of these properties, BoHV-4 has been successfully developed as a veterinary vaccine vector in model animal species against a variety of infectious diseases. BoHV-4-vectored vaccines have successfully induced neutralizing antibody responses to bovine herpesvirus-1 (BoHV-1) and Bovine Viral Diarrhea Virus (BVDV) type 1 in rabbits [11, 12], neutralizing antibody responses to BVDV type 1 in sheep [13], neutralizing antibody responses to Bluetongue virus and to Peste de Petits Ruminants (PPR) virus in mice, respectively [14, 15], and protective viral neutralizing antibody responses against caprine herpesvirus-1 in goats [16]. Despite the success of the BoHV-4 platform in these non-BoHV-4 host species, and the intrinsic benefits of the BoHV-4 platform, immunization using BoHV-4 has never been attempted in cattle.…”

Vaccination With Recombinant Adenoviruses Expressing the Bluetongue Virus Subunits VP7 and VP2 Provides Protection Against Heterologous Virus Challenge

“…Splenocytes (4–5 × 10 6 /well in 24-well plates) from immunized animals were stimulated in vitro with VP7(283) peptide [VP7(283–291) TAILNRTTL; 10 μg/ml] for 6 days and used as effector cells in flow cytometry-based cytotoxicity assays. Syngenic RMA/S cells pulsed as previously described ( 40 ) with 10 μg/ml of relevant peptide VP7(283) or irrelevant peptide NS1(152) [NS1(152–160) GQIVNPTFI] from BTV [known to elicit T-cell responses in IFNAR (−/−) mice ( 22 , 26 )] were used as target cells. Target cells were labeled with PKH67 dye as described in Rojas et al ( 41 ), and cytotoxicity was performed as previously described in Rojas et al ( 42 ).…”

A New Look at Vaccine Strategies Against PPRV Focused on Adenoviral Candidates

“…The H and F glycoproteins are the principal targets of neutralizing antibodies of the humoral immune response. These two glycoproteins have been considered the best to include in vaccine candidates and their genes have been cloned and expressed in several recombinant, replication-defective viral vectors: (i) Poxviruses ( 39 , 40 ), (ii), Bovine-Herpes viruses ( 43 ), (iii) Newcastle disease virus ( 44 ), and (iv) Adenoviruses ( 33 , 34 , 36 , 37 , 68 ).…”