Luo Jun, Zhang Boyue, Wu Yuting, Tian Qin, Zhao Jing, Lyu Ziyu, Zhang Qiong, Mei Mingzhu, Luo Yongwen, Guo Xiaofeng
College of Veterinary Medicine, South China Agricultural University, Guangzhou, China; Key Laboratory of Zoonosis Prevention and Control of Guangdong Province, China.
College of Veterinary Medicine, South China Agricultural University, Guangzhou, China; Key Laboratory of Zoonosis Prevention and Control of Guangdong Province, China.
Vaccine. 2017 Feb 7;35(6):938-944. doi: 10.1016/j.vaccine.2016.12.069. Epub 2017 Jan 12.
Several studies have confirmed that interleukin-6 (IL6) mediates multiple biological effects that enhance immune responses when used as an adjuvant. In the present study, recombinant rabies virus (RABV) expressing canine IL6 (rHEP-CaIL6) was rescued and its pathogenicity and immunogenicity were investigated in mice. We demonstrated that mice received a single intramuscular immunization with rHEP-CaIL6 showed an earlier increase and higher maximum titres of virus-neutralizing antibody (VNA) as well as anti-RABV antibodies compared with mice immunized with the parent strain. Moreover, survival rates of mice immunized with rHEP-CaIL6 were higher compared with mice immunized with parent HEP-Flury according to the challenge assay. Flow cytometry further confirmed that immunization with rHEP-CaIL6 induced the strong recruitment of mature B cells and CD8 T cells to lymph nodes, which may partially explain the high levels of VNA and enhanced cellular immunity. Quantitative real-time PCR indicated that rHEP-CaIL6 induced stronger inflammatory and immune responses in the central nervous system, which might have allowed virus clearance in the early infection phase. Furthermore, mice infected intranasally with rHEP-CaIL6 developed no clinical symptoms while mice infected with HEP-Flury showed piloerection. In summary, these data indicate that rHEP-CaIL6 induces a strong, protective immune response with a good safety profile. Therefore, a recombinant RABV strain expressing canine IL6 may aid the development of an effective, safe attenuated rabies vaccine.
多项研究证实，白细胞介素-6（IL6）作为佐剂时可介导多种增强免疫反应的生物学效应。在本研究中，拯救出了表达犬IL6的重组狂犬病病毒（RABV，rHEP-CaIL6），并在小鼠中研究了其致病性和免疫原性。我们证明，与用亲本毒株免疫的小鼠相比，用rHEP-CaIL6进行单次肌肉注射免疫的小鼠，病毒中和抗体（VNA）以及抗狂犬病病毒抗体的水平升高更早且峰值更高。此外，根据攻毒试验，用rHEP-CaIL6免疫的小鼠的存活率高于用亲本HEP-Flury免疫的小鼠。流式细胞术进一步证实，用rHEP-CaIL6免疫可诱导成熟B细胞和CD8 T细胞大量募集至淋巴结，这可能部分解释了VNA水平高以及细胞免疫增强的原因。定量实时PCR表明，rHEP-CaIL6在中枢神经系统中诱导了更强的炎症和免疫反应，这可能有助于在感染早期清除病毒。此外，经鼻内感染rHEP-CaIL6的小鼠未出现临床症状，而感染HEP-Flury的小鼠出现竖毛现象。总之，这些数据表明，rHEP-CaIL6可诱导强烈的保护性免疫反应，且安全性良好。因此，表达犬IL6的重组RABV毒株可能有助于开发有效、安全的减毒狂犬病疫苗。
