Protective immunity following vaccination with a recombinant multiple-epitope protein of bovine herpesvirus type I in a rabbit model.

Bovine herpesvirus type 1 (BoHV-1) causes considerable economic losses to the cow industry. Vaccination remains an effective strategy to control the diseases associated with BoHV-1. However, live vaccines present safety concerns, especially in pregnant cows; thus, nonreplicating vaccines have been developed to control the disease. The envelope glycoproteins of BoHV-1 induce a protective immune response. In this work, selected epitopes on glycoproteins gD, gC, and gB were constructed in triplicate with linker peptides. Vaccination of rabbits demonstrated that P2-gD/gC/gB with AAYAAY induced higher specific antibodies than that with GGGGS linker. P2-gD/gC/gB with AAYAAY linker was fused with bovine interleukin-6 (BoIL-6) or rabbit IL-6 (RaIL-6) and bacterially expressed. Rabbits were intramuscularly immunized with 100 µg of P2-gD/gC/gB-BoIL-6, P2-gD/gC/gB-RaIL-6, P2-gD/gC/gB, P2-gD/gC/gB plus BoIL-6, P2-(gD-a)3-BoIL-6, or P2-(gD-a)3 emulsified with ISA 206 adjuvant thrice at 3-week intervals. P2-gD/gC/gB-BoIL-6 generated a higher titer of BoHV-1-specific antibodies, neutralizing antibodies, interferon (IFN)-γ, and IL-4 compared with P2-gD/gC/gB plus BoIL-6, P2-gD/gC/gB-RaIL-6, or other formulation. P2-gD/gC/gB-BoIL-6 triggered similar levels of antibodies and significantly higher titer of IFN-γ and IL-4 compared with inactivated bovine viral diarrhea (BVD)-infectious bovine rhinotracheitis (IBR) vaccine. Rabbits vaccinated with P2-gD/gC/gB-BoIL-6 dramatically reduced viral shedding and tissue lesions in lungs and trachea after viral challenge and reactivation compared with those with P2-gD/gC/gB plus BoIL-6 or P2-gD/gC/gB-RaIL-6. P2-gD/gC/gB-BoIL-6 provided protective effects against viral shedding and tissue pathogenesis similar to those of the inactivated vaccine. The data confirmed the safety and immunogenicity of multiple-epitope recombinant protein and a potential vaccine candidate to control the disease, especially for pregnant cattle.

Mapping a highly conserved linear neutralizing epitope on gD glycoprotein of bovine herpesvirus type I using a monoclonal antibody.

Bovine herpesvirus type 1 (BoHV-1), a member of the Alphaherpesvirinae, causes a variety of diseases, which result in significant economic losses worldwide. Envelope glycoprotein D (gD) of BoHV-1 plays an important role in viral entry into the permissive cells, and protective immune response. The fine mapping epitope on the gD will contribute to the understanding of viral pathogenesis and development of alternative vaccines against various diseases associated with BoHV-1. We previously reported the preparation of a monoclonal antibody (MAb) 2B6, which was raised by a truncated recombinant gD protein, demonstrating a neutralizing activity against BoHV-1 infection in Madin-Darby bovine kidney cells. This study described the identification of a linear B-cell epitope on gD using MAb 2B6. A series of partially overlapping gD proteins with glutathione S-transferase tag were generated to define the epitope recognized by MAb 2B6. The amino acid (aa) sequence 323GEPKPGPSPDADRPE337 was recognized by MAb 2B6 using Western blot with the variedly truncated recombinant proteins. Importantly, this epitope was highly conserved among the typical members of BoHV-1, indicating that the epitope may be utilized in diagnosis of diseases due to BoHV-1 infection. Furthermore, the minimal linear epitope sequence 323GEPKPGP329 on gD recognized by MAb 2B6 was confirmed using single-aa residue deletion mutation in carboxyl terminal. This finding not only contributes to our understanding of gD of BoHV-1 virion but also shows a potential for the development of vaccine candidates and diagnostic techniques.

A systematic review and meta-analysis of the epidemiology of bovine viral diarrhea virus (BVDV) infection in dairy cattle in China.

Bovine viral diarrhea virus (BVDV) infection causes significantly economic losses to cattle industry worldwide, also including China. The epidemiological prevalence of infection associated with BVDV in dairy cattle has not been systematically assessed in China. Therefore, we undertook this study to evaluate prevalent of BVDV infection. We conducted a systematic review and meta-analysis of data from papers on the BVDV incidence and prevalence in dairy cattle in China by searching China Science and Technology Journal Database, China National Knowledge Infrastructure (CNKI), Wan Fang Database and PubMed for publication from March 2003 to March 2018. The 41 studies reporting the prevalence of BVDV in cattle in China were selected upon our inclusion criterion. The pooled BVDV prevalence in dairy cattle in China was estimated to 53.0% (95% CI 40.2-65.7) based on the data obtained from the 27,530 cows tested using serological or virological assay in the qualified papers published during the periods (χ² = 51,861.0, I2 = 99.9%). The highest BVDV positive rate in dairy flocks reached 90.0% in Fujian province of China, followed by Shaanxi (88.9%) and Shandong (83.3%). The prevalence in the six administrative districts of China was validated to be highly variable (25.7%-72.2%) and reached 72.2% in dairy cattle flocks of Northern China. Besides, the BVDV-RNA positive rate was estimated 27.1% (95% CI 17.3-37.0) based on 6 studies, comparatively, the pooled BVDV seroprevalence based on 35 studies was about 57.0% (95% CI 44.4-69.5) in China. This systematic review and meta-analysis firstly established an estimated prevalence of BVDV in dairy herds in China, indicating that the BVDV infection is escalating, though there is a bias in the number of studies between 2003-2009 and 2010-2018 timescales. This study may help understand the status of BVDV infection in dairy herds in China. Further extensive and comprehensive investigation is recommended, and effective intervention measures for preventing and controlling BVDV spread in dairy herds should be deployed, especially herds that have been exposed to BVDV.