Plug-and-Display: decoration of Virus-Like Particles via isopeptide bonds for modular immunization

被引：318

作者：

Brune, Karl D. ^{[1
]}

Leneghan, Darren B. ^{[2
]}

Brian, Iona J. ^{[2
]}

Ishizuka, Andrew S. ^{[2
]}

Bachmann, Martin F. ^{[2
,3
]}

Draper, Simon J. ^{[2
]}

Biswas, Sumi ^{[2
]}

Howarth, Mark ^{[1
]}

机构：

[1] Univ Oxford, Dept Biochem, Oxford OX1 3QU, England

[2] Univ Oxford, Jenner Inst, Oxford OX3 7DQ, England

[3] Univ Bern, Univ Inst Immunol, CH-3010 Bern, Switzerland

来源：

SCIENTIFIC REPORTS | 2016年 / 6卷

基金：

英国惠康基金;

关键词：

ESCHERICHIA-COLI; PROTEIN; VACCINE; FUNCTIONALIZATION; SPYCATCHER; ANTIBODIES; MOLECULES; INFECTION; RESPONSES; SEQUENCE;

D O I：

10.1038/srep19234

中图分类号：

O [数理科学和化学]; P [天文学、地球科学]; Q [生物科学]; N [自然科学总论];

学科分类号：

070301 [无机化学]; 070403 [天体物理学]; 070507 [自然资源与国土空间规划学]; 090105 [作物生产系统与生态工程];

摘要：

Virus-like particles (VLPs) are non-infectious self-assembling nanoparticles, useful in medicine and nanotechnology. Their repetitive molecularly-defined architecture is attractive for engineering multivalency, notably for vaccination. However, decorating VLPs with target-antigens by genetic fusion or chemical modification is time-consuming and often leads to capsid misassembly or antigen misfolding, hindering generation of protective immunity. Here we establish a platform for irreversibly decorating VLPs simply by mixing with protein antigen. SpyCatcher is a genetically-encoded protein designed to spontaneously form a covalent bond to its peptide-partner SpyTag. We expressed in E. coli VLPs from the bacteriophage AP205 genetically fused to SpyCatcher. We demonstrated quantitative covalent coupling to SpyCatcher-VLPs after mixing with SpyTag-linked to malaria antigens, including CIDR and Pfs25. In addition, we showed coupling to the VLPs for peptides relevant to cancer from epidermal growth factor receptor and telomerase. Injecting SpyCatcher-VLPs decorated with a malarial antigen efficiently induced antibody responses after only a single immunization. This simple, efficient and modular decoration of nanoparticles should accelerate vaccine development, as well as other applications of nanoparticle devices.

引用

页数：13

共 72 条

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