Kang Hongtao, Qi Yinglin, Wang Hualei, Zheng Xuexing, Gao Yuwei, Li Nan, Yang Songtao, Xia Xianzhu
College of Veterinary Medicine, South China Agricultural University, 483 Wushan Road, Guangzhou 510642, China.
Institute of Military Veterinary Medicine, Academy of Military Medical Science, 666 Liuying West Road, Changchun 130122, China.
Viruses. 2015 Mar 11;7(3):1134-52. doi: 10.3390/v7031134.
Rabies remains an important public health threat in most developing countries. To develop a more effective and safe vaccine against rabies, we have constructed a chimeric rabies virus-like particle (VLP), which containing glycoprotein (G) and matrix protein (M) of rabies virus (RABV) Evelyn-Rokitnicki-Abelseth (ERA) strain, and membrane-anchored granulocyte-macrophage colony-stimulating factor (GM-CSF), and it was named of EVLP-G. The immunogenicity and protective efficacy of EVLP-G against RABV were evaluated by intramuscular administration in a mouse model. The EVLP-G was successfully produced in insect cells by coinfection with three recombinant baculoviruses expressing G, M, and GM-CSF, respectively. The membrane-anchored GM-CSF possesses a strong adjuvant activity. More B cells and dendritic cells (DCs) were recruited and/or activated in inguinal lymph nodes in mice immunized with EVLP-G. EVLP-G was found to induce a significantly increased RABV-specific virus-neutralizing antibody and elicit a larger and broader antibody subclass responses compared with the standard rabies VLP (sRVLP, consisting of G and M). The EVLP-G also elicited significantly more IFN-γ- or IL-4-secreting CD4+ and CD8+ T cells than the sRVLP. Moreover, the immune responses induced by EVLP-G protect all vaccinated mice from lethal challenge with RABV. These results suggest that EVLP-G has the potential to be developed as a novel vaccine candidate for the prevention and control of animal rabies.
在大多数发展中国家，狂犬病仍然是一个重要的公共卫生威胁。为了研发一种更有效、更安全的狂犬病疫苗，我们构建了一种嵌合狂犬病病毒样颗粒（VLP），它包含狂犬病病毒（RABV）伊夫林-罗基特尼基-阿贝尔塞思（ERA）株的糖蛋白（G）和基质蛋白（M），以及膜锚定的粒细胞-巨噬细胞集落刺激因子（GM-CSF），并将其命名为EVLP-G。通过在小鼠模型中肌肉注射来评估EVLP-G对RABV的免疫原性和保护效力。通过分别与三种表达G、M和GM-CSF的重组杆状病毒共感染，EVLP-G在昆虫细胞中成功产生。膜锚定的GM-CSF具有很强的佐剂活性。在用EVLP-G免疫的小鼠腹股沟淋巴结中，募集和/或激活了更多的B细胞和树突状细胞（DC）。与标准狂犬病VLP（sRVLP，由G和M组成）相比，发现EVLP-G能诱导显著增加的RABV特异性病毒中和抗体，并引发更大范围和更广泛的抗体亚类反应。与sRVLP相比，EVLP-G还能显著诱导更多分泌IFN-γ或IL-4的CD4+和CD8+ T细胞。此外，EVLP-G诱导的免疫反应能保护所有接种疫苗的小鼠免受RABV的致死性攻击。这些结果表明，EVLP-G有潜力被开发成为一种用于预防和控制动物狂犬病的新型候选疫苗。
