SnoopLigase peptide-peptide conjugation enables modular vaccine assembly
Autor: | Can M. Buldun, Anne-Marie C. Andersson, David J. Pattinson, Simon J. Draper, Mark Howarth |
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Jazyk: | angličtina |
Rok vydání: | 2019 |
Předmět: |
0301 basic medicine
Telomerase Immunoconjugates medicine.medical_treatment lcsh:Medicine Antigens Protozoan Peptide Computational biology Article 03 medical and health sciences Synthetic biology 0302 clinical medicine Antigen Cancer immunotherapy medicine Adhesins Bacterial lcsh:Science chemistry.chemical_classification Antigens Bacterial Vaccines Isopeptide bond Multidisciplinary Vaccination lcsh:R 3. Good health Bacterial adhesin Streptococcus pneumoniae 030104 developmental biology chemistry Nanoparticles lcsh:Q Peptides 030217 neurology & neurosurgery Conjugate |
Zdroj: | Scientific Reports, Vol 9, Iss 1, Pp 1-13 (2019) Scientific Reports |
ISSN: | 2045-2322 |
Popis: | For many infectious diseases there is still no vaccine, even though potential protective antigens have been identified. Suitable platforms and conjugation routes are urgently needed to convert the promise of such antigens into broadly protective and scalable vaccines. Here we apply a newly established peptide-peptide ligation approach, SnoopLigase, for specific and irreversible coupling of antigens onto an oligomerization platform. SnoopLigase was engineered from a Streptococcus pneumoniae adhesin and enables isopeptide bond formation between two peptide tags: DogTag and SnoopTagJr. We expressed in bacteria DogTag linked to the self-assembling coiled-coil nanoparticle IMX313. This platform was stable over months at 37 °C when lyophilized, remaining reactive even after boiling. IMX-DogTag was efficiently coupled to two blood-stage malarial proteins (from PfEMP1 or CyRPA), with SnoopTagJr fused at the N- or C-terminus. We also showed SnoopLigase-mediated coupling of a telomerase peptide relevant to cancer immunotherapy. SnoopLigase-mediated nanoassembly enhanced the antibody response to both malaria antigens in a prime-boost model. Including or depleting SnoopLigase from the conjugate had little effect on the antibody response to the malarial antigens. SnoopLigase decoration represents a promising and accessible strategy for modular plug-and-display vaccine assembly, as well as providing opportunities for robust nanoconstruction in synthetic biology. |
Databáze: | OpenAIRE |
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