Poster Presentation 14th Australian Peptide Conference 2022

Peptide-based therapeutic nanovaccine against cervical cancer (#202)

Waleed M Hussein 1 , Tzu-Yu Liu 1 , Pirashanthini Maruthayanar 2 , Saori Mukaida 1 , Peter M Moyle 3 , James W Wells 2 , Istvan Toth 1 3 4 , Mariusz Skwarczynski 1
  1. School of Chemistry and Molecular Biosciences, The University of Queensland, St Lucia, QLD, Australia
  2. The University of Queensland Diamantina Institute, The University of Queensland, Brisbane, QLD, Australia
  3. School of Pharmacy, The University of Queensland, Brisbane, QLD, Australia
  4. Institute for Molecular Bioscience, The University of Queensland, Brisbane, QLD, Australia

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).

 

References
1. W.M. Hussein, S. Mukaida, F. Azmi, S. Bartlett, C. Olivier, M.R. Batzloff, M.F. Good, M. Slovarczynski, I. Toth, Comparison of Fluorinated and Nonfluorinated Lipids in Self-Adjuvanting Delivery Systems for Peptide-Based Vaccines, Acs Medicinal Chemistry Letters 8 (2017) 227-232.
2. W.M. Hussein, T.Y. Liu, P. Maruthayanar, S. Mukaida, P.M. Moyle, J.W. Wells, I. Toth, M. Skwarczynski, Double conjugation strategy to incorporate lipid adjuvants into multiantigenic vaccines, Chemical Science 7 (2016) 2308-2321.
3. T.Y. Liu, W.M. Hussein, A.K. Giddam, Z. Jia, J.M. Reiman, M. Zaman, N.A. McMillan, M.F. Good, M.J. Monteiro, I. Toth, M. Skwarczynski, Polyacrylate-Based Delivery System for Self-adjuvanting Anticancer Peptide Vaccine, J Med Chem 58 (2015) 888-96.
4. T.Y. Liu, A.K. Giddam, W.M. Hussein, Z.F. Jia, N.A.J. McMillan, M.J. Monteiro, I. Toth, M. Skwarczynski, Self-Adjuvanting Therapeutic Peptide-Based Vaccine Induce CD8(+) Cytotoxic T Lymphocyte Responses in a Murine Human Papillomavirus Tumor Model, Current Drug Delivery 12 (2015) 3-8.
5. T.-Y. Liu, W.M. Hussein, Z. Jia, Z.M. Ziora, N.A.J. McMillan, M.J. Monteiro, I. Toth, M. Skwarczynski, Self-Adjuvanting Polymer-Peptide Conjugates As Therapeutic Vaccine Candidates against Cervical Cancer, Biomacromolecules 14 (2013) 2798-2806.