Journal article
Peptide mimic for influenza vaccination using nonnatural combinatorial chemistry
JJ Miles, MP Tan, G Dolton, ESJ Edwards, SAE Galloway, B Laugel, M Clement, J Makinde, K Ladell, KK Matthews, TS Watkins, K Tungatt, Y Wong, HS Lee, RJ Clark, JM Pentier, M Attaf, A Lissina, A Ager, A Gallimore Show all
Journal of Clinical Investigation | AMER SOC CLINICAL INVESTIGATION INC | Published : 2018
DOI: 10.1172/JCI91512
Abstract
Polypeptide vaccines effectively activate human T cells but suffer from poor biological stability, which confines both transport logistics and in vivo therapeutic activity. Synthetic biology has the potential to address these limitations through the generation of highly stable antigenic "mimics" using subunits that do not exist in the natural world. We developed a platform based on D-amino acid combinatorial chemistry and used this platform to reverse engineer a fully artificial CD8+ T cell agonist that mirrored the immunogenicity profile of a native epitope blueprint from influenza virus. This nonnatural peptide was highly stable in human serum and gastric acid, reflecting an intrinsic resi..
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Awarded by Health and Care Research Wales
Funding Acknowledgements
This study was made possible by a Biotechnology and Biological Sciences Research Council (BBSRC) Strategic Longer Larger Grant (BB/H001085/1) and further Sparking Impact funding from the BBSRC. Additional support was provided by the Cardiff Synthetic Biology Initiative through SynbiCITE, a Perpetual Research Grant (FR2013/0946), and the Medical Research Council (United Kingdom). JJM and MPT received personal funding from the National Institute of Social Care and Health Research (now Health and Care Research Wales). RJC and SG are supported by Australian Research Council Future Fellowships (FT100100476 and FF120100416). DAP and AKS are Wellcome Trust Senior Investigators. JJM is supported by the Australian National Health and Medical Research Council (NHMRC). JR is supported by an Australian Research Council Laureate Fellowship.