Engineering a Rugged Nanoscaffold To Enhance Plug-and-Display Vaccination.
Engineering a Rugged Nanoscaffold To Enhance Plug-and-Display Vaccination.
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DOI：
10.1021/acsnano.8b02805
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发表时间：
2018-09-25
期刊：
影响因子：
17.1
通讯作者：
Howarth M
中科院分区：
文献类型：
--
作者：
Bruun TUJ;Andersson AC;Draper SJ;Howarth M
纳米级的组织对于使用自组装蛋白作为多媒体平台刺激免疫响应至关重要。尚不清楚合成蛋白纳米仪是否会显示出类似的效力。设计了多孔的十二面体i301 60-mer，并理性地设计了该粒子，从而使i301（MI3）具有改善的粒子均匀性和稳定性，以简化该纳米粒子的缀合，我们采用了MI3的间谍融合对间谍肽可以自发地通过异肽键形成（插头）。大肠杆菌的产量超过10倍以上，比噬菌体的二十面体纳米颗粒，spycatcher-ap205。将抗原抗原耦合到不同的传播阻滞和疟原虫。尽管具有较高的价值和RNA货物，但引起了高自然抗体反应，与噬菌体衍生的病毒样颗粒相当。
Nanoscale organization is crucial to stimulating an immune response. Using self-assembling proteins as multimerization platforms provides a safe and immunogenic system to vaccinate against otherwise weakly immunogenic antigens. Such multimerization platforms are generally based on icosahedral viruses and have led to vaccines given to millions of people. It is unclear whether synthetic protein nanoassemblies would show similar potency. Here we take the computationally designed porous dodecahedral i301 60-mer and rationally engineer this particle, giving a mutated i301 (mi3) with improved particle uniformity and stability. To simplify the conjugation of this nanoparticle, we employ a SpyCatcher fusion of mi3, such that an antigen of interest linked to the SpyTag peptide can spontaneously couple through isopeptide bond formation (Plug-and-Display). SpyCatcher-mi3 expressed solubly to high yields in Escherichia coli, giving more than 10-fold greater yield than a comparable phage-derived icosahedral nanoparticle, SpyCatcher-AP205. SpyCatcher-mi3 nanoparticles showed high stability to temperature, freeze–thaw, lyophilization, and storage over time. We demonstrate approximately 95% efficiency coupling to different transmission-blocking and blood-stage malaria antigens. Plasmodium falciparum CyRPA was conjugated to SpyCatcher-mi3 nanoparticles and elicited a high avidity antibody response, comparable to phage-derived virus-like particles despite their higher valency and RNA cargo. The simple production, precise derivatization, and exceptional ruggedness of this nanoscaffold should facilitate broad application for nanobiotechnology and vaccine development.
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DOI：
10.4161/hv.5.1.6494
发表时间：
2009-01-01
期刊：
HUMAN VACCINES
影响因子：
--
作者：
Chen, Dexiang;Tyagi, Anil;Braun, LaToya Jones
通讯作者：
Braun, LaToya Jones
影响因子：
7
作者：
Alving CR;Peachman KK;Rao M;Reed SG
通讯作者：
Reed SG
DOI：
10.1107/s0907444903013192
发表时间：
2003-08-01
影响因子：
2.2
作者：
Bell, BJ;Watanabe, L;Arni, RK
通讯作者：
Arni, RK
影响因子：
2.2
作者：
AIDA, Y;PABST, MJ
通讯作者：
PABST, MJ
影响因子：
64.8
作者：
Butterfield GL;Lajoie MJ;Gustafson HH;Sellers DL;Nattermann U;Ellis D;Bale JB;Ke S;Lenz GH;Yehdego A;Ravichandran R;Pun SH;King NP;Baker D
通讯作者：
Baker D