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

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

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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.

Item Type:

Journal Article (Original Article)

Division/Institute:

04 Faculty of Medicine > Department of Dermatology, Urology, Rheumatology, Nephrology, Osteoporosis (DURN) > Clinic of Rheumatology, Clinical Immunology and Allergology

UniBE Contributor:

Bachmann, Martin

Subjects:

600 Technology > 610 Medicine & health

ISSN:

2045-2322

Publisher:

Nature Publishing Group

Language:

English

Submitter:

Nathalie Taiana

Date Deposited:

29 Feb 2016 16:18

Last Modified:

26 Jun 2016 02:11

Publisher DOI:

10.1038/srep19234

PubMed ID:

26781591

BORIS DOI:

10.7892/boris.76236

URI:

https://boris.unibe.ch/id/eprint/76236

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