Ou Huilin, Yao Wei, Yu Dongshan, Weng Tianhao, Wang Frederick X C, Wu Xiaoxin, Wu Haibo, Cheng Linfang, Lu Xiangyun, Wu Nanping, Chen Honglin, Li Lanjuan, Yao Hangping
State Key Laboratory for Diagnosis and Treatment of Infectious Diseases, Collaborative Innovation Center for Diagnosis and Treatment of Infectious Diseases, The First Affiliated Hospital, Zhejiang University School of Medicine, Hangzhou, China.
Zhejiang Tianyuan Bio-Pharmaceutical Co., Ltd., Hangzhou, China.
Oncotarget. 2017 Aug 8;8(54):91828-91840. doi: 10.18632/oncotarget.20064. eCollection 2017 Nov 3.
The influenza virus is a serious threat to public health worldwide. A novel avian influenza A (H7N9) virus with a mortality rate of approximately 30% has been identified as an unusually dangerous virus for humans by the World Health Organization. Pathogenic H7N9 continue to represent a public health concern, and several candidate vaccines are currently in development. We generated candidate H7N9 vaccine strains using reverse genetics, consisting of hemagglutinin and neuraminidase genes derived from a human H7N9 virus and the remaining genes from the PR8 (A/PuertoRico/8/34 (H1N1)) virus. This H7N9 vaccine exhibited superior efficacy when combined with MF59 compared to other adjuvants. Immunized BALB/c mice were followed to determine the duration of the protective immune response. Antibody levels decreased to between one-half and one-eighth of the peak values four months after the final dose of the vaccine. Previously vaccinated mice received an A/Zhejiang/DTID-ZJU01/2013 H7N9 challenge six months post-vaccination, and all remained protected. We also verified that MF59 enhanced the HI, MN, and IgG antibody titers to influenza antigens. The humoral immune response and Th2 cytokine production following influenza challenge was potently induced in the animals that received the split vaccine. Therefore, the split H7N9 influenza vaccine with the MF59 adjuvant could effectively induce antibody production and protect mice from H7N9 virus challenge even after six months.
流感病毒对全球公共卫生构成严重威胁。一种死亡率约为30%的新型甲型H7N9禽流感病毒被世界卫生组织确定为对人类异常危险的病毒。致病性H7N9仍然是一个公共卫生问题,目前有几种候选疫苗正在研发中。我们利用反向遗传学方法构建了候选H7N9疫苗株,其血凝素和神经氨酸酶基因来源于一株人H7N9病毒,其余基因来自PR8(A/波多黎各/8/34(H1N1))病毒。与其他佐剂相比,这种H7N9疫苗与MF59联合使用时表现出更高的效力。对免疫的BALB/c小鼠进行跟踪,以确定保护性免疫反应的持续时间。在最后一剂疫苗接种四个月后,抗体水平降至峰值的二分之一至八分之一之间。先前接种过疫苗的小鼠在接种疫苗六个月后接受A/浙江/DTID-ZJU01/2013 H7N9攻击,所有小鼠均受到保护。我们还证实,MF59提高了对流感抗原的血凝抑制(HI)、微量中和(MN)和IgG抗体滴度。在接受裂解疫苗的动物中,流感攻击后可有效诱导体液免疫反应和Th2细胞因子产生。因此,含有MF59佐剂的裂解H7N9流感疫苗即使在六个月后也能有效诱导抗体产生,并保护小鼠免受H7N9病毒攻击。