Newcastle disease virus-like particles containing the Brucella BCSP31 protein induce dendritic cell activation and protect mice against virulent Brucella challenge

• Published in: Veterinary microbiology Vol. 229; pp. 39 - 47
• Main Authors: Xu, Xiaohong, Ding, Zhuang, Li, Jindou, Liang, Jiaming, Bu, Zhaoyang, Ding, Jiaxin, Yang, Yanling, Lang, Xulong, Wang, Xinglong, Yin, Renfu, Qian, Jing
• Format: Journal Article
• Language: English
• Published: Netherlands Elsevier B.V 01-02-2019; Elsevier BV
• Subjects: Brucella; Brucella BCSP31 protein; Brucellosis; CD3 antigen; CD4 antigen; CD8 antigen; Cell activation; Dendritic cell maturation; Dendritic cells; Enzyme-linked immunosorbent assay; Glycosylphosphatidylinositol; Health risks; Immune response (cell-mediated); Interleukin 4; Lymphocytes; Lymphocytes T; M protein; Newcastle disease; Newcastle disease virus-like particles; Protective efficacy; Proteins; Public health; Vaccine candidate; Vaccines; Virus-like particles; Zoonoses; γ-Interferon; Protective efficacy; Dendritic cell maturation; Vaccine candidate; Newcastle disease virus-like particles; Brucella BCSP31 protein
• ISSN: 0378-1135; 1873-2542
• DOI: 10.1016/j.vetmic.2018.12.007

•A NDV VLP based Brucella vaccine candidate was developed.•The Brucella antigen BCSP31 was linked to VLPs through a GPI modifying strategy.•The cVLPs proved its sufficient DCs activating ability in vivo and in vitro.•The cVLPs conferred full protection against the virulent B. melitensis strain 16 M.
Brucellosis is a widespread zoonosis that poses a substantial threat to human and animal public health due to the absence of a sufficiently safe and efficient vaccine. Virus-like particles (VLPs) have been developed as novel vaccine candidates and suitable carrier platforms for the delivery of exogenous proteins. Herein, we constructed chimeric virus-like particles (cVLPs) assembled by a Newcastle disease virus (NDV) M protein and glycosylphosphatidylinositol-anchored Brucella BCSP31 protein (GPI-BCSP31). cVLPs-GPI-BCSP31 were highly efficient in murine dendritic cell (DC) activation, both in vitro and in vivo. Moreover, they elicited strong specific humoural immune responses detected through ELISA assay with inactivated Brucella and recombinant BCSP31 protein and by elevated cellular immune responses indicated by intracellular IFN-γ and IL-4 levels in CD3+CD4+ T and CD3+CD8+ T cells. Importantly, cVLPs-GPI-BCSP31 conferred protection against virulent Brucella melitensis strain 16 M challenge, comparable to the efficacy of Brucella vaccine strain M5. In summary, this study provides a new strategy for the development of a safe and effective vaccine candidate against virulent Brucella and further extends the application of NDV VLP-based vaccine platforms.