Virus-like particles vaccines based on glycoprotein E0 and E2 of bovine viral diarrhea virus induce Humoral responses

Abstract

Bovine viral diarrhea/mucosal disease (BVD/MD) is a viral infectious disease that seriously endangers the health of cattle herds and brings serious economic losses to the global cattle industry. Virus-like particles (VLPs) are empty shell structures without viral nucleic acid, which are similar to natural virus particles in morphology and structure. Because of their strong immunogenicity and biological activity, some of them have been used as vaccines in clinical trials. In this study, we developed a strategy to generate BVDV (E0 + E2, E2 + E2) VLPs using an insect baculovirus expression vector system (BEVS). The VLPs obtained were detected by immunofluorescence assay (IFA), western blotting analyses and transmission electron microscope (TEM), and the results showed that VLPs of high purity were obtained. Mice immunized with VLPs (15 μg) and Freund’s adjuvant (100 μl) elicited higher BVDV-neutralizing antibody in comparison with Freund’s adjuvant control (p < 0.0001), and even on day 21 or 35 post-prime immunization, the neutralizing antibody levels of mice immunized with E0 + E2 or E2 + E2 VLPs were significantly higher compared with inactivated vaccine (p < 0.05). A subsequent challenge reveals that the viral loads of livers, kidneys, spleens, lungs and small intestines were significantly lower compared with control (p < 0.0001), and the viral loads of mice immunized with E0 + E2 or E2 + E2 VLPs in the small intestines were significantly lower compared with inactivated vaccine (p < 0.05). Thus, VLPs are a promising candidate vaccine and warrants further clinical evaluation.

Diagnosis of bovine viral diarrhea virus: an overview of currently available methods

“…Bedeković et al developed an IFA method for the diagnosis of BVDV in which a specific monoclonal antibody for BVDV was used as primary antibody and an anti-mouse antibody conjugated with fluorescein isothiocyanate (FITC) as secondary antibody. The IFA assay showed a sensitivity and specificity of 100% in detecting 9 positive samples when compared to the RT-PCR assay (Bedeković et al, 2011) of E0 + E2 and E2 + E2 were subsequently detected by immunofluorescence assay (IFA) and western blot (Yang N. et al, 2022). In another experiment, the IFA was applied to detect a positive BVDV-3 strain using BVDV-positive serum as primary antibody and FITC-labeled rabbit anti-bovine IgG as secondary antibody.…”

Detection of emerging HoBi-like Pestivirus (BVD-3) during an epidemiological investigation of bovine viral diarrhea virus in Xinjiang: a first-of-its-kind report

“…BVDV is a member of the Flaviviridae family, belonging to the Pestivirus genus together with classical swine fever virus (CSFV) and border disease virus (BDV; Chen et al, 2021 ; Yang et al, 2022 ). According to the recommendations of the Flaviviridae Study Group of the International Committee on Taxonomy of Viruses (ICTV), BVDV can be divided into three genotypes: BVDV-1 ( Pestivirus A), BVDV-2 ( Pestivirus B), and atypical Pestivirus or BVDV-3 ( Pestivirus H; Smith et al, 2017 ).…”

“…BVDV can be divided into cytopathic (CP) and non-cytopathic (NCP) types, depending on whether they can cause cytopathic effect (CPE) on host cells, and both biotypes are pathogenic. However, only NCP strains can cause persistent infection (PI) in cattle ( Lackner et al, 2004 ; Yang et al, 2022 ). The existence of PI cattle is also one of the major reasons why BVDV is difficult to prevent and eliminate.…”