杆状病毒展示的血凝素对高致病性H7亚型流感病毒的交叉保护效力。
Cross-protective efficacy of baculovirus displayed hemagglutinin against highly pathogenic influenza H7 subtypes.
作者信息
Prabakaran Mookkan, Kumar Subaschandrabose Rajesh, Raj Kattur Venkatachalam Ashok, Wu Xiapeng, He Fang, Zhou JiYong, Kwang Jimmy
机构信息
Animal Health Biotechnology, Temasek Life Sciences Laboratory, National University of Singapore, 117604, Singapore.
Animal Health Biotechnology, Temasek Life Sciences Laboratory, National University of Singapore, 117604, Singapore; Key Laboratory of Animal Virology of Ministry of Agriculture, Zhejiang University, Hangzhou 310058, PR China.
出版信息
Antiviral Res. 2014 Sep;109:149-59. doi: 10.1016/j.antiviral.2014.06.017. Epub 2014 Jul 2.
The outbreak of human infections with avian-origin H7N9 influenza has raised global concerns about a potential human pandemic. Therefore, the generation of simple and reliable newer vaccines is high priority for pandemic preparedness. In this study, we aimed to develop a recombinant vaccine by expressing HA of H7N9 (A/Shanghai/2/2013) on the surface of baculovirus (BacHA). Further, live or inactive form of BacHA (H7N9) vaccine was immunized twice either intranasally or subcutaneously into mice. The immunogenicity and cross-protective efficacy of the BacHA (H7N9) vaccine was assessed against H7N9 or H7N7 subtype challenge. The results showed that mice immunized subcutaneously with adjuvanted inactive BacHA (H7N9) induced robust cross-neutralizing antibody responses against H7 subtypes (H7N9, H7N7 and H7N3) compared to subcutaneous or intranasal immunization of live BacHA. In contrast, mice immunized intranasally with live BacHA stimulated higher HA-specific mucosal IgA levels in the upper airways, the port of virus entry. Also, intranasal immunization of BacHA of either H7N9 or H7N7 completely protected against 5 MLD50 of both H7N9 and H7N7 infections. An overall study revealed that intranasal administration of HA expressed on the baculovirus envelope is alternative way to prime the immune system against influenza infection during a pandemic situation.
人感染H7N9禽流感疫情引发了全球对潜在大流行的担忧。因此,研发简单可靠的新型疫苗是大流行防范的重中之重。在本研究中,我们旨在通过在杆状病毒表面表达H7N9(A/上海/2/2013)的血凝素(BacHA)来开发一种重组疫苗。此外,将活的或灭活形式的BacHA(H7N9)疫苗经鼻内或皮下途径对小鼠进行两次免疫。评估了BacHA(H7N9)疫苗针对H7N9或H7N7亚型攻击的免疫原性和交叉保护效力。结果表明,与皮下或鼻内免疫活的BacHA相比,皮下免疫佐剂灭活的BacHA(H7N9)的小鼠诱导了针对H7亚型(H7N9、H7N7和H7N3)的强大交叉中和抗体反应。相反,经鼻内免疫活的BacHA的小鼠在上呼吸道(病毒进入部位)刺激了更高的血凝素特异性黏膜IgA水平。此外,经鼻内免疫H7N9或H7N7的BacHA可完全保护小鼠免受5个半数致死剂量(MLD50)的H7N9和H7N7感染。一项全面研究表明,在大流行情况下,经鼻内给予杆状病毒包膜上表达的血凝素是启动免疫系统抵抗流感感染的另一种方式。