Centre de Recerca en Sanitat Animal, UAB-IRTA, Campus de la Universitat Autònoma de Barcelona, 08193 Bellaterra, Spain.
Vaccine. 2012 Mar 23;30(14):2427-39. doi: 10.1016/j.vaccine.2012.01.069. Epub 2012 Feb 3.
Virus-like particles (VLPs) have received considerable attention due to their potential application in veterinary vaccines and, in particular, VLPs from rabbit haemorrhagic disease virus (RHDV) have successfully shown to be good platforms for inducing immune responses against an inserted foreign epitope in mice. The aim of this study was to assess the immunogenicity of chimeric RHDV-VLPs as vaccine vectors in pigs. For this purpose, we have generated chimeric VLPs containing a well-known T epitope of 3A protein of foot-and-mouth disease virus (FMDV). Firstly, RHDV-VLPs were able to activate immature porcine bone marrow-derived dendritic cells (poBMDCs) in vitro. Secondly, pigs were inoculated twice in a two-week interval with chimeric RHDV-VLPs at different doses intranasally or intramuscularly. One intramuscularly treated group was also inoculated with adjuvant Montanide™ ISA 206 at the same time. Specific IgG and IgA antibodies against RHDV-VLPs were induced and such levels were higher in the adjuvanted group compared with other groups. Interestingly, anti-RHDV-VLP IgA responses were higher in groups inoculated intramuscularly than those that received the VLPs intranasally. Two weeks after the last immunisation, specific IFN-γ-secreting cells against 3A epitope and against RHDV-VLPs were detected in PBMCs by ELISPOT. The adjuvanted group exhibited the highest IFN-γ-secreting cell numbers and lymphoproliferative specific T cell responses against 3A epitope and RHDV-VLP. This is the first immunological report on the potential use of chimeric RHDV-VLPs as antigen carriers in pigs.
病毒样颗粒(VLPs)因其在兽医疫苗中的潜在应用而受到广泛关注,特别是兔出血症病毒(RHDV)的 VLPs 已成功证明是在小鼠中诱导针对插入的外源表位的免疫应答的良好平台。本研究旨在评估嵌合 RHDV-VLPs 作为疫苗载体在猪中的免疫原性。为此,我们生成了含有口蹄疫病毒(FMDV) 3A 蛋白的已知 T 表位的嵌合 VLP。首先,RHDV-VLPs 能够在体外激活不成熟的猪骨髓来源树突状细胞(poBMDCs)。其次,猪在两周的间隔内两次通过鼻内或肌肉内接种不同剂量的嵌合 RHDV-VLPs。同一肌肉内处理组也同时用佐剂 Montanide™ISA 206 接种。诱导了针对 RHDV-VLPs 的特异性 IgG 和 IgA 抗体,并且在佐剂组中的水平高于其他组。有趣的是,与接受 VLPs 鼻内接种的组相比,肌肉内接种组的抗 RHDV-VLP IgA 反应更高。最后一次免疫接种后两周,通过 ELISPOT 在 PBMC 中检测到针对 3A 表位和 RHDV-VLP 的特异性 IFN-γ 分泌细胞。佐剂组表现出针对 3A 表位和 RHDV-VLP 的最高 IFN-γ 分泌细胞数和淋巴增殖特异性 T 细胞反应。这是关于嵌合 RHDV-VLPs 作为抗原载体在猪中潜在用途的第一个免疫学报告。