Vaccination against H9N2 avian influenza virus reduces bronchus-associated lymphoid tissue formation in cynomolgus macaques after intranasal virus challenge infection
Vaccination against H9N2 avian influenza virus reduces bronchus-associated lymphoid tissue formation in cynomolgus macaques after intranasal virus challenge infection
复制标题
H9N2禽流感病毒疫苗接种可减少食蟹猴鼻内病毒攻击感染后支气管相关淋巴组织的形成
DOI：
10.1111/pin.12472
复制
发表时间：
2016
影响因子：
2.2
通讯作者：
Ogasawara K
中科院分区：
文献类型：
--
作者：
Nakayama M;Ozaki H;Itoh Y;Soda K;Ishigaki H;Okamatsu M;Sakoda Y;Park C-H;Tsuchiya H;Kida H;Ogasawara K
H9 N2禽流感病毒引起散发性人类感染。由于人类不具备对这种病毒的获得性免疫力，我们检查了从人类分离的H9 N2病毒的致病性，然后分析了疫苗在食蟹猴中的保护作用。在用从人类患者分离的A/Hong Kong/1073/1999（H9 N2）（HK 1073）进行鼻内攻毒后，从未接种疫苗的猕猴的鼻和气管拭子中分离出病毒，这些猕猴出现轻度发热和体重减轻。将来自我们的病毒库的福尔马林灭活的H9 N2全颗粒疫苗皮下接种至猕猴。疫苗接种诱导血清中的病毒抗原特异性IgG和中和活性。在用H9 N2鼻内攻击后，仅在接种疫苗的猕猴中接种后第二天检测到病毒。在未接种疫苗的情况下，感染后在肺部形成了许多支气管相关淋巴组织（BALT），而接种疫苗的猕猴中BALT的数量较少，细胞因子反应弱于未接种疫苗的猕猴。这些发现表明，H9 N2禽流感病毒HK 1073在灵长类动物中具有致病性，但似乎比我们先前研究中发现的H7N9流感病毒引起的症状更轻，并且福尔马林灭活的H9 N2全颗粒疫苗诱导针对H9 N2病毒的保护性免疫。
H9N2 avian influenza virus causes sporadic human infection. Since humans do not possess acquired immunity specific to this virus, we examined the pathogenicity of an H9N2 virus isolated from a human and then analyzed protective effects of a vaccine in cynomolgus macaques. After intranasal challenge with A/Hong Kong/1073/1999 (H9N2) (HK1073) isolated from a human patient, viruses were isolated from nasal and tracheal swabs in unvaccinated macaques with mild fever and body weight loss. A formalin‐inactivated H9N2 whole particle vaccine derived from our virus library was subcutaneously inoculated to macaques. Vaccination induced viral antigen‐specific IgG and neutralization activity in sera. After intranasal challenge with H9N2, the virus was detected only the day after inoculation in the vaccinated macaques. Without vaccination, many bronchus‐associated lymphoid tissues (BALTs) were formed in the lungs after infection, whereas the numbers of BALTs were smaller and the cytokine responses were weaker in the vaccinated macaques than those in the unvaccinated macaques. These findings indicate that the H9N2 avian influenza virus HK1073 is pathogenic in primates but seems to cause milder symptoms than does H7N9 influenza virus as found in our previous studies and that a formalin‐inactivated H9N2 whole particle vaccine induces protective immunity against H9N2 virus.