Ou Huilin, Yao Wei, Wu Nanping, Wang Frederick X C, Weng Tianhao, Han Chengcong, Lu Xiangyun, Yu Dongshan, Wu Haibo, Cheng Linfang, Chen Honglin, Yao Hangping, Li Lanjuan
State Key Laboratory for Diagnosis and Treatment of Infectious Diseases, Collaborative Innovation Center for Diagnosis and Treatment of Infectious Diseases, The First Affiliated Hospital, School of Medicine, Zhejiang University, Hangzhou, China.
Department of Pre-clinical Research and Development, Zhejiang Tianyuan Bio-Pharmaceutical Co., Ltd., Hangzhou, China.
Oncotarget. 2016 Dec 6;7(49):81012-81025. doi: 10.18632/oncotarget.12746.
Developing a safe and effective H7N9 influenza vaccine was initiated in early spring 2013, following human infections with a novel avian influenza A (H7N9) virus. In this study, a candidate H7N9 vaccine seed strain is produced using reverse genetics, with HA and NA derived from a human H7N9 virus and the remaining genes from the PR8 backbone virus which grows well in eggs. We verified that the virulence and transmissibility of the recombinant H7N9 vaccine seed strain were decreased as compared to wild-type H7N9 virus, to levels comparable with PR8. Using the seed virus, we produced a monovalent split influenza A (H7N9) MF59-adjuvanted vaccine that was immunogenic in mice. Our H7N9 vaccine is selected for clinical investigation and potential human use. To assess the safety of our H7N9 vaccine, we performed acute toxicity, repeated dose toxicity and active systemic anaphylaxis tests. Our results showed that, under the conditions used in this study, the NOEAL (no obvious adverse effect level) was 30 μg/0.5 mL.
在人感染新型甲型禽流感（H7N9）病毒后，于2013年早春开始研发安全有效的H7N9流感疫苗。在本研究中，利用反向遗传学方法制备了一种候选H7N9疫苗种子株，其血凝素（HA）和神经氨酸酶（NA）来源于一株人H7N9病毒，其余基因来自在鸡胚中生长良好的PR8骨架病毒。我们证实，与野生型H7N9病毒相比，重组H7N9疫苗种子株的毒力和传播性降低至与PR8相当的水平。利用该种子病毒，我们制备了一种单价裂解甲型流感（H7N9）MF59佐剂疫苗，该疫苗在小鼠中具有免疫原性。我们的H7N9疫苗被选用于临床研究和潜在的人体使用。为评估我们的H7N9疫苗的安全性，我们进行了急性毒性、重复剂量毒性和主动全身过敏试验。我们的结果表明，在本研究使用的条件下，无明显不良作用水平（NOAEL）为30μg/0.5mL。
