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


Autoria(s): Brune, Karl D; Leneghan, Darren B; Brian, Iona J; Ishizuka, Andrew S; Bachmann, Martin; Draper, Simon J; Biswas, Sumi; Howarth, Mark
Data(s)

2016

Resumo

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.

Formato

application/pdf

Identificador

http://boris.unibe.ch/76236/1/srep19234.pdf

Brune, Karl D; Leneghan, Darren B; Brian, Iona J; Ishizuka, Andrew S; Bachmann, Martin; Draper, Simon J; Biswas, Sumi; Howarth, Mark (2016). Plug-and-Display: decoration of Virus-Like Particles via isopeptide bonds for modular immunization. Scientific Reports, 6(19234), p. 19234. Nature Publishing Group 10.1038/srep19234 <http://dx.doi.org/10.1038/srep19234>

doi:10.7892/boris.76236

info:doi:10.1038/srep19234

info:pmid:26781591

urn:issn:2045-2322

Idioma(s)

eng

Publicador

Nature Publishing Group

Relação

http://boris.unibe.ch/76236/

Direitos

info:eu-repo/semantics/openAccess

Fonte

Brune, Karl D; Leneghan, Darren B; Brian, Iona J; Ishizuka, Andrew S; Bachmann, Martin; Draper, Simon J; Biswas, Sumi; Howarth, Mark (2016). Plug-and-Display: decoration of Virus-Like Particles via isopeptide bonds for modular immunization. Scientific Reports, 6(19234), p. 19234. Nature Publishing Group 10.1038/srep19234 <http://dx.doi.org/10.1038/srep19234>

Palavras-Chave #610 Medicine & health
Tipo

info:eu-repo/semantics/article

info:eu-repo/semantics/publishedVersion

PeerReviewed