新型牛病毒性腹泻病毒（BVDV）病毒样颗粒疫苗候选物利用 SpyTag/SpyCatcher 系统展示 E2 蛋白，可在小鼠中诱导出强大的中和抗体反应。

Novel bovine viral diarrhea virus (BVDV) virus-like particle vaccine candidates presenting the E2 protein using the SpyTag/SpyCatcher system induce a robust neutralizing antibody response in mice.

机构信息

Laboratory of Environmental Microbiology, Faculty of Medicine, University of Tsukuba, 1-1-1 Tennodai, Tsukuba, Ibaraki, 305-8575, Japan.

Exotic Disease Research Group, National Institute of Animal Health, National Agriculture and Food Research Organization (NARO), 6-20-1 Josuihoncho, Kodaira, Tokyo, 187-0022, Japan.

出版信息

Arch Virol. 2023 Jan 7;168(2):49. doi: 10.1007/s00705-022-05653-x.

DOI:10.1007/s00705-022-05653-x

PMID:36609880

原文链接:https://pmc.ncbi.nlm.nih.gov/articles/PMC9825097/

Abstract

Bovine viral diarrhea virus (BVDV) is a pathogen of commercial consequence in cattle. Although many modified live and killed vaccines are commercially available, their drawbacks precipitate the need for new effective vaccines. Virus-like particles (VLPs) are a safe and powerful technology used in several human and veterinary vaccines; however, it is difficult to produce large amounts of BVDV VLPs. In this study, we generated red-spotted grouper nervous necrosis virus (RGNNV) VLPs presenting the BVDV E2 protein (domain I to IIIb) of the Nose (BVDV-1) or KZ-91-CP (BVDV-2) strain by exploiting SpyTag/SpyCatcher technology. Mice immunized twice with 30 μg of RGNNV VLPs conjugated with 10 μg of E2 proteins of the Nose or KZ-91-CP strain with a 14-day interval elicited high (1:512,000 to 1:1,024,000) and moderate (1:25,600 to 1:102,400) IgG titers against E2 proteins of homologous and heterologous strains, respectively. In addition, this prime-boost regimen induced strong (1:800 to 1:3,200) and weak (~1:10) neutralization titers against homologous and heterologous BVDV strains, respectively. Our results indicate that conjugation of the E2 protein to RGNNV VLPs strongly enhances the antigenicity of the E2 protein and that RGNNV VLPs presenting the E2 protein are promising BVDV vaccine candidates.

摘要

牛病毒性腹泻病毒（BVDV）是一种对牛具有商业重要性的病原体。尽管有许多改良的活疫苗和死疫苗可供商业使用，但它们的缺点促使人们需要新的有效疫苗。病毒样颗粒（VLPs）是一种安全有效的技术，已应用于几种人类和兽医疫苗中；然而，大量生产 BVDV VLPs 是困难的。在这项研究中，我们利用 SpyTag/SpyCatcher 技术生成了 presenting 有 BVDV Nose（BVDV-1）或 KZ-91-CP（BVDV-2）株的 E2 蛋白（I 至 IIIb 结构域）的红鳍东方鲀神经坏死病毒（RGNNV）VLPs。用 30μg 与 Nose 或 KZ-91-CP 株的 E2 蛋白（10μg）偶联的 RGNNV VLPs 对小鼠进行两次免疫，间隔 14 天，可引起针对同源和异源株 E2 蛋白的高（1:512000 至 1:1024000）和中（1:25600 至 1:102400）IgG 滴度。此外，这种初免-加强免疫方案诱导了针对同源和异源 BVDV 株的强（1:800 至 1:3200）和弱（~1:10）中和滴度。我们的结果表明，E2 蛋白与 RGNNV VLPs 的偶联强烈增强了 E2 蛋白的抗原性，并且 presenting 有 E2 蛋白的 RGNNV VLPs 是有前途的 BVDV 疫苗候选物。