Yong Chean Yeah, Yeap Swee Keong, Ho Kok Lian, Omar Abdul Rahman, Tan Wen Siang
Department of Microbiology, Faculty of Biotechnology and Biomolecular Sciences, Universiti Putra Malaysia, Selangor, Malaysia.
Institute of Bioscience, Faculty of Medicine and Health Sciences, Universiti Putra Malaysia, Selangor, Malaysia.
Int J Nanomedicine. 2015 Apr 2;10:2751-63. doi: 10.2147/IJN.S77405. eCollection 2015.
Influenza A virus poses a major threat to human health, causing outbreaks from time to time. Currently available vaccines employ inactivated viruses of different strains to provide protection against influenza virus infection. However, high mutation rates of influenza virus hemagglutinin (H) and neuraminidase (N) glycoproteins give rise to vaccine escape mutants. Thus, an effective vaccine providing protection against all strains of influenza virus would be a valuable asset. The ectodomain of matrix 2 protein (M2e) was found to be highly conserved despite mutations of the H and N glycoproteins. Hence, one to five copies of M2e were fused to the carboxyl-terminal end of the recombinant nodavirus capsid protein derived from Macrobrachium rosenbergii. The chimeric proteins harboring up to five copies of M2e formed nanosized virus-like particles approximately 30 nm in diameter, which could be purified easily by immobilized metal affinity chromatography. BALB/c mice immunized subcutaneously with these chimeric proteins developed antibodies specifically against M2e, and the titer was proportional to the copy numbers of M2e displayed on the nodavirus capsid nanoparticles. The fusion proteins also induced a type 1 T helper immune response. Collectively, M2e displayed on the nodavirus capsid nanoparticles could provide an alternative solution to a possible influenza pandemic in the future.
甲型流感病毒对人类健康构成重大威胁，不时引发疫情。目前可用的疫苗采用不同毒株的灭活病毒来预防流感病毒感染。然而，流感病毒血凝素（H）和神经氨酸酶（N）糖蛋白的高突变率会产生疫苗逃逸突变体。因此，一种能预防所有流感病毒毒株的有效疫苗将是一项宝贵资产。尽管H和N糖蛋白发生了突变，但基质2蛋白（M2e）的胞外域被发现高度保守。因此，将一至五个M2e拷贝融合到源自罗氏沼虾的重组诺达病毒衣壳蛋白的羧基末端。携带多达五个M2e拷贝的嵌合蛋白形成了直径约30纳米的纳米级病毒样颗粒，可通过固定化金属亲和色谱轻松纯化。用这些嵌合蛋白皮下免疫的BALB/c小鼠产生了针对M2e的特异性抗体，且滴度与诺达病毒衣壳纳米颗粒上展示的M2e拷贝数成正比。融合蛋白还诱导了1型辅助性T细胞免疫反应。总体而言，展示在诺达病毒衣壳纳米颗粒上的M2e可为未来可能的流感大流行提供一种替代解决方案。
