Double conjugation strategy to incorporate lipid adjuvants into multiantigenic vaccines. Issue 3 (13th January 2016)

• Record Type: Journal Article
• Authors: Hussein, Waleed M.; Liu, Tzu-Yu; Maruthayanar, Pirashanthini; Mukaida, Saori; Moyle, Peter M.; Wells, James W.; Toth, Istvan; Skwarczynski, Mariusz
• Is Part Of: Chemical science. Volume 7:Issue 3(2016:Mar.)
• Page Start: 2308
• Page End: 2321
• Publication Date: 2016-01-13
• Subjects: Chemistry -- Periodicals; 540.5
• DOI: 10.1039/c5sc03859f
• Languages: English
• ISSNs: 2041-6520

Abstract

Abstract : Conjugation of multiple peptides by their N-termini is a promising technique to produce branched multiantigenic vaccines. 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).