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Double conjugation strategy to incorporate lipid adjuvants into 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).

SUBMITTER: Hussein WM

PROVIDER: S-EPMC5977935 | biostudies-literature | 2016 Mar

REPOSITORIES: biostudies-literature

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Double conjugation strategy to incorporate lipid adjuvants into multiantigenic vaccines.

Hussein Waleed M WM Liu Tzu-Yu TY Maruthayanar Pirashanthini P Mukaida Saori S Moyle Peter M PM Wells James W JW Toth Istvan I Skwarczynski Mariusz M

Chemical science 20160104 3

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 moiet ...[more]

PMID: 29910921

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