Wu Xiao-Xin, Deng Xi-Long, Yu Dong-Shan, Yao Wei, Ou Hui-Lin, Weng Tian-Hao, Hu Chen-Yu, Hu Feng-Yu, Wu Nan-Ping, Yao Hangping, Zhang Fu-Chun, Li Lan-Juan
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.
Guangzhou Eighth People's Hospital, Guangzhou Medical University, Guangzhou, China.
Cell Physiol Biochem. 2018;46(2):633-643. doi: 10.1159/000488631. Epub 2018 Mar 28.
BACKGROUND/AIMS: Since the first case of novel H7N9 infection was reported, China has experienced five epidemics of H7N9. During the fifth wave, a highly pathogenic H7N9 strain emerged. In order to assess whether the H7N9 vaccine based on A/Zhejiang/DTID-ZJU01/2013(H7N9) was effective in protecting against highly pathogenic H7N9, we conducted this study.
Groups of mice were immunized twice by intraperitoneal injection with 500 µl of either split vaccine alone or MF59-adjuvanted vaccine. Serum was collected 2 weeks after the second vaccine booster. The hemagglutinin inhibition test was conducted on vaccine seed and highly pathogenic H7N9 to evaluate the neutralization of highly pathogenic H7N9. We also immunized mice and challenged them with highly pathogenic H7N9. Mice were observed for illness, weight loss, and death at 1 week and 2 weeks post-infection. Then, the mice were sacrificed and lungs were removed. Antibody responses were assessed and pathological changes in the lung tissue were evaluated.
The ability of serum to neutralize highly pathogenic H7N9 was reduced. In mice, highly pathogenic H7N9 was more virulent than A/Zhejiang/DTID-ZJU01/2013(H7N9). After challenge with highly pathogenic H7N9, all mice died while mice challenged with A/Zhejiang/DTID-ZJU01/2013(H7N9) all recovered. The A/ZJU01/PR8/2013 split H7N9 avian influenza vaccine was able to protect against infection with highly pathogenic H7N9 in mice, with or without MF59. Moreover, H7N9 vaccine adjuvanted with MF59 produced high antibody levels, which lead to better protection.
The A/ZJU01/PR8/2013 split H7N9 avian influenza vaccine based on A/Zhejiang/DTID-ZJU01/2013(H7N9) is effective in protecting against highly pathogenic H7N9. H7N9 vaccine adjuvanted with MF59 offers better protection against infection with highly pathogenic H7N9. In order to make the H7N9 vaccine applicable to humans, further clinical trials are required to evaluate MF59 adjuvanted vaccine. Meanwhile, the vaccine strain should be updated based on the highly pathogenic H7N9 gene sequence.
背景/目的：自首例新型H7N9感染病例报告以来，中国已经历了5次H7N9疫情。在第五波疫情期间，出现了一种高致病性H7N9毒株。为了评估基于A/浙江/DTID-ZJU01/2013(H7N9)的H7N9疫苗对高致病性H7N9的防护效果，我们开展了本研究。
将小鼠分组，通过腹腔注射500μl单独的裂解疫苗或含MF59佐剂的疫苗进行两次免疫。在第二次疫苗加强免疫后2周采集血清。对疫苗种子和高致病性H7N9进行血凝抑制试验，以评估对高致病性H7N9的中和作用。我们还对小鼠进行免疫并使其感染高致病性H7N9。在感染后1周和2周观察小鼠的发病情况、体重减轻情况和死亡情况。然后，处死小鼠并取出肺脏。评估抗体反应并评价肺组织的病理变化。
血清中和高致病性H7N9的能力降低。在小鼠中，高致病性H7N9比A/浙江/DTID-ZJU01/2013(H7N9)的毒性更强。在用高致病性H7N9攻击后，所有小鼠死亡，而用A/浙江/DTID-ZJU01/2013(H7N9)攻击的小鼠全部康复。A/ZJU01/PR8/2013裂解H7N9禽流感疫苗无论有无MF59都能够保护小鼠免受高致病性H7N9的感染。此外，含MF59佐剂的H7N9疫苗产生了高水平抗体，从而带来了更好的保护效果。
基于A/浙江/DTID-ZJU01/2013(H7N9)的A/ZJU01/PR8/2013裂解H7N9禽流感疫苗对高致病性H7N9具有防护效果。含MF59佐剂的H7N9疫苗对高致病性H7N9感染提供了更好的保护。为使H7N9疫苗适用于人类，需要进一步开展临床试验以评估含MF59佐剂的疫苗。同时，应根据高致病性H7N9基因序列更新疫苗毒株。
