Development of a novel dual-domain nanoparticle antigen construct for universal influenza vaccine.
Development of a novel dual-domain nanoparticle antigen construct for universal influenza vaccine.
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DOI：
10.1016/j.vaccine.2017.10.051
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发表时间：
2017-12-15
期刊：
影响因子：
5.5
通讯作者：
Tizard I
中科院分区：
文献类型：
--
作者：
Ni Y;Guo J;Turner D;Tizard I
用于呈递保守抗原结构域的高效抗原构建体对于开发通用流感疫苗是必不可少的。我们已经开发了一种新的双结构域纳米颗粒融合蛋白（DDNFP），它允许独立的两个保守结构域的介绍。使用的保守结构域来自两种单独的病毒表面蛋白，M2的M2 e和HA 2的融合肽（FP）或长α螺旋（CD）。该载体是一种新的纳米颗粒蛋白-来自细菌或古细菌的饥饿细胞（Dps）的十二聚体DNA结合蛋白。发现Dps独特地能够在N-和C-末端同时融合和表面呈递，同时保留形成纳米颗粒的能力。因此，具有M2 e和FP或CD的DDNFP在来自E.首先基于H1亚型序列沿着相应的单结构域纳米颗粒融合蛋白（SDNFP）构建大肠杆菌（EcDps）或其它细菌。它们在细菌中以高水平表达，并形成预期大小（约9 nm）的纳米颗粒。它们对高温处理是稳定的。DDNFP（M2 e-EcDps-FP和M2 e-EcDps-CD）诱导针对单个抗原结构域的强抗体应答，并提供针对PR 8病毒（H1N1）致死攻击的完全保护。重要的是，与SDNFP相比，DDNFP的保护作用协同增强。M2 e-EcDps-CD提供了比M2 e-EcDps-FP更强的保护，因此似乎是上级构建体。结合新的结构域组合、增强的保护和易于生产，这种M2 e/CD DDNFP可能是用于通用流感疫苗的高效抗原构建体。
A highly effective antigen construct for presenting conserved antigen domains is essential to the development of a universal influenza vaccine. We have developed a novel dual-domain nanoparticle fusion protein (DDNFP) which allows independent presentation of two conserved domains. The conserved domains used were from two separate viral surface proteins, M2e of M2 and fusion peptide (FP) or long alpha helix (CD) of HA2. The carrier is a novel nanoparticle protein - the dodecameric DNA binding protein from starved cells (Dps) of bacteria or archaea. Dps was found to be uniquely capable of simultaneous fusion and surface presentation at both N- and C-termini while retaining the ability to form nanoparticles. Thus, DDNFPs with M2e and FP or CD fused at N- and C- termini of Dps from E. coli (EcDps) or other bacteria were first constructed based on the H1 subtype sequences along with corresponding single-domain nanoparticle fusion proteins (SDNFPs). They were expressed at high levels in bacteria and found to form nanoparticles of the expected size (~9 nm). They were stable against treatment at high temperatures. The DDNFPs (M2e-EcDps-FP and M2e-EcDps-CD) induced strong antibody responses against individual antigen domains and provided full protection against lethal challenge with PR8 virus (H1N1). Importantly, the protection by DDNFPs was synergistically enhanced as compared to SDNFPs. The M2e-EcDps-CD provided an even stronger protection than M2e-EcDps-FP and therefore appeared to be the superior construct. Together, with novel domain combination, enhanced protection and ease of production, this M2e/CD DDNFP could potentially be a highly effective antigen construct for the universal influenza vaccine.
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DOI：
10.1186/cc2955
发表时间：
2004-10
期刊：
Critical care (London, England)
影响因子：
--
作者：
Bewick V;Cheek L;Ball J
通讯作者：
Ball J
影响因子：
82.9
作者：
Neirynck, S;Deroo, T;Fiers, W
通讯作者：
Fiers, W
影响因子：
8
作者：
通讯作者：
--
影响因子：
5.5
作者：
Chun, Stella;Li, Changgui;Li, Xuguang
通讯作者：
Li, Xuguang
DOI：
10.1073/pnas.0813167106
发表时间：
2009-02-10
影响因子：
11.1
作者：
Rath, Arianna;Glibowicka, Mira;Deber, Charles M.
通讯作者：
Deber, Charles M.