Double conjugation strategy to incorporate lipid adjuvants into multiantigenic vaccines

Hussein, Waleed M., Liu, Tzu-Yu, Maruthayanar, Pirashanthini, Mukaida, Saori, Moyle, Peter M., Wells, James W., Toth, Istvan and Skwarczynski, Mariusz (2016) Double conjugation strategy to incorporate lipid adjuvants into multiantigenic vaccines. Chemical Science, 7 3: 2308-2321. doi:10.1039/C5SC03859F


Author Hussein, Waleed M.
Liu, Tzu-Yu
Maruthayanar, Pirashanthini
Mukaida, Saori
Moyle, Peter M.
Wells, James W.
Toth, Istvan
Skwarczynski, Mariusz
Title Double conjugation strategy to incorporate lipid adjuvants into multiantigenic vaccines
Journal name Chemical Science   Check publisher's open access policy
ISSN 2041-6520
2041-6539
Publication date 2016-01-04
Year available 2016
Sub-type Article (original research)
DOI 10.1039/C5SC03859F
Open Access Status DOI
Volume 7
Issue 3
Start page 2308
End page 2321
Total pages 14
Place of publication Cambridge, United Kingdom
Publisher Royal Society of Chemistry
Language eng
Subject 1600 Chemistry
Abstract Conjugation of multiple peptides by their N-termini is a promising technique to produce branched multiantigenic vaccines. We established a double conjugation strategy that combines a mercapto-acryloyl Michael addition and a copper-catalysed alkyne-azide 1,3-dipolar cycloaddition (CuAAC) reaction to synthesise self-adjuvanting branched multiantigenic vaccine candidates. These vaccine candidates aim to treat cervical cancer and include two HPV-16 derived epitopes and a novel self-adjuvanting moiety. This is the first report of mercapto-acryloyl conjugation applied to the hetero conjugation of two unprotected peptides by their N-termini followed by a CuAAC reaction to conjugate a novel synthetic lipoalkyne self-adjuvanting moiety. In vivo experiments showed that the most promising vaccine candidate completely eradicated tumours in 46% of the mice (6 out of 13 mice).
Keyword Chemistry, Multidisciplinary
Chemistry
Q-Index Code C1
Q-Index Status Provisional Code
Grant ID NHMRC 1006454
Institutional Status UQ

Document type: Journal Article
Sub-type: Article (original research)
Collections: HERDC Pre-Audit
School of Chemistry and Molecular Biosciences
School of Pharmacy Publications
UQ Diamantina Institute Publications
 
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Created: Thu, 14 Jan 2016, 19:44:49 EST by Peter Moyle on behalf of School of Pharmacy