Imperial College London
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DrJuliaMakinde

Faculty of Medicine, Department of Infectious Disease

Honorary Lecturer
 
 
 
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Contact

 

j.makinde

 
 
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Location

 

Chelsea and Westminster HospitalChelsea and Westminster Campus

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Summary

 

Publications

Citation

BibTex format

@article{Miles:2018:10.1172/JCI91512,
author = {Miles, JJ and Tan, MP and Dolton, G and Edwards, ESJ and Galloway, SAE and Laugel, B and Clement, M and Makinde, J and Ladell, K and Matthews, KK and Watkins, TS and Tungatt, K and Wong, Y and Lee, HS and Clark, RJ and Pentier, JM and Attaf, M and Lissina, A and Ager, A and Gallimore, A and Rizkallah, PJ and Gras, S and Rossjohn, J and Burrows, SR and Cole, DK and Price, DA and Sewell, AK},
doi = {10.1172/JCI91512},
journal = {JOURNAL OF CLINICAL INVESTIGATION},
pages = {1569--1580},
title = {Peptide mimic for influenza vaccination using nonnatural combinatorial chemistry},
url = {http://dx.doi.org/10.1172/JCI91512},
volume = {128},
year = {2018}
}
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RIS format (EndNote, RefMan)

TY  - JOUR
AB  - 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 resistance to physical and enzymatic degradation. In vitro, the synthetic agonist stimulated and expanded an archetypal repertoire of polyfunctional human influenza virus–specific CD8+ T cells. In vivo, specific responses were elicited in naive humanized mice by subcutaneous vaccination, conferring protection from subsequent lethal influenza challenge. Moreover, the synthetic agonist was immunogenic after oral administration. This proof-of-concept study highlights the power of synthetic biology to expand the horizons of vaccine design and therapeutic delivery.
AU  - Miles,JJ
AU  - Tan,MP
AU  - Dolton,G
AU  - Edwards,ESJ
AU  - Galloway,SAE
AU  - Laugel,B
AU  - Clement,M
AU  - Makinde,J
AU  - Ladell,K
AU  - Matthews,KK
AU  - Watkins,TS
AU  - Tungatt,K
AU  - Wong,Y
AU  - Lee,HS
AU  - Clark,RJ
AU  - Pentier,JM
AU  - Attaf,M
AU  - Lissina,A
AU  - Ager,A
AU  - Gallimore,A
AU  - Rizkallah,PJ
AU  - Gras,S
AU  - Rossjohn,J
AU  - Burrows,SR
AU  - Cole,DK
AU  - Price,DA
AU  - Sewell,AK
DO  - 10.1172/JCI91512
EP  - 1580
PY  - 2018///
SN  - 0021-9738
SP  - 1569
TI  - Peptide mimic for influenza vaccination using nonnatural combinatorial chemistry
T2  - JOURNAL OF CLINICAL INVESTIGATION
UR  - http://dx.doi.org/10.1172/JCI91512
UR  - http://gateway.webofknowledge.com/gateway/Gateway.cgi?GWVersion=2&SrcApp=PARTNER_APP&SrcAuth=LinksAMR&KeyUT=WOS:000431958600034&DestLinkType=FullRecord&DestApp=ALL_WOS&UsrCustomerID=1ba7043ffcc86c417c072aa74d649202
UR  - http://hdl.handle.net/10044/1/60604
VL  - 128
ER  -
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