Induction of Robust and Specific Humoral and Cellular Immune Responses by Bovine Viral Diarrhea Virus Virus-Like Particles (BVDV-VLPs) Engineered with Baculovirus Expression Vector System.

Zhanhui Wang,Yunke Zhang,Mengyao Liu,Wenge Ma,Haoran Zhao,Wenxue Wu,Pengpeng Wang,Chen Peng

doi:10.3390/vaccines9040350

Zhanhui Wang, Yunke Zhang + Show 6 more

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https://doi.org/10.3390/vaccines9040350

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Journal: Vaccines	Publication Date: Apr 6, 2021
Citations: 11	License type: CC BY 4.0

Affiliation: China Agricultural University

Abstract

Bovine viral diarrhea virus (BVDV) is an important animal pathogen that affects cattle. Infections caused by the virus have resulted in substantial economic losses and outbreaks of BVDV are reported globally. Virus-like particles (VLPs) are promising vaccine technology largely due to their safety and strong ability to elicit robust immune responses. In this study, we developed a strategy to generate BVDV-VLPs using a baculovirus expression vector system (BEVS). We were able to assemble BVDV-VLPs composed of dimerized viral proteins E2 and Erns, and the VLPs were spherical particles with the diameters of about 50 nm. Mice immunized with 15 μg of VLPs adjuvanted with ISA201 elicited higher levels of E2-specific IgG, IgG1, and IgG2a antibodies as well as higher BVDV-neutralizing activity in comparison with controls. Re-stimulation of the splenocytes collected from mice immunized with VLPs led to significantly increased levels of CD3+CD4+T cells and CD3+CD8+T cells. In addition, the splenocytes showed dramatically enhanced proliferation and the secretion of Th1-associated IFN-γ and Th2-associated IL-4 compared to that of the unstimulated control group. Taken together, our data indicate that BVDV-VLPs efficiently induced BVDV-specific humoral and cellular immune responses in mice, showing a promising potential of developing BVDV-VLP-based vaccines for the prevention of BVDV infections.

Highlights

Bovine viral diarrhea virus (BVDV) is an important pathogen of cattle found in many parts of the world, which poses a great threat to agriculture globally
The baculovirus gp64 signal peptide was fused to the N-terminal ends of Erns and E2; the gp64-Erns and gp64-E2 were inserted into pFastBac Dual vector to generate the recombinant plasmid pFastBac-Erns +E2 and the subsequent recombinant bacmid rBacmidsErns +E2
The results showed that vaccination of mice with BVDV-Virus-like particles (VLPs) induced significantly higher levels of IgG, IgG1, and IgG2a antibodies against BVDV E2 protein compared to controls in the presence of adjuvant (Figure 6A–C)

Summary

Introduction

Bovine viral diarrhea virus (BVDV) is an important pathogen of cattle found in many parts of the world, which poses a great threat to agriculture globally. BVDV is capable of infecting a diverse range of animals, including pigs, sheep, goats, deer, and camelids [1]. BVDV often induces both acute infections (AI) and persistent infections (PI). Symptoms associated with AI include diarrhea, fever, leukopenia, coughing, and increased nasal discharge. PI is established when a non-cytopathic (NCP) BVDV crosses the barrier of placenta and infects an immunoincompetent fetus. Infected calves are the major source to spread BVDV as they can shed virus throughout their lives, and viruses can be detected in almost all organs [2,3] from these calves

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