Poster Presentation 14th Australian Peptide Conference 2022

Peptide-based nanoparticle adjuvant induces balanced Th1/Th2 immune responses against co-administered antigens (#217)

Harrison Y.R. Madge 1 , Wenbin Huang 1 , Waleed M. Hussein 1 , Zeinab G. Khalil 2 , Prashamsa Koirala 1 , Robert J. Capon 2 , Istvan Toth 1 2 3 , Rachel J. Stephenson 1
  1. School of Chemistry and Molecular Biosciences, The University of Queensland, Brisbane, Queensland, Australia
  2. Institute of Molecular Biosciences, The University of Queensland, Brisbane, Queensland, Australia
  3. School of Pharmacy, The University of Queensland, Brisbane, Queensland, Australia

The progress of modern vaccine research, specifically the development of peptide-based vaccine technology, is predominantly governed by the lack of safe and effective adjuvants. To date, most commercially available adjuvants are particularly ineffective at stimulating immune responses to short peptide-based antigens. A current solution for inducing immune responses against short peptides is the display of peptide epitopes on self-adjuvanting delivery systems incorporating synthetic toll-like receptor ligands. We have recently demonstrated that co-assembly of peptide epitopes with a lipopeptide based adjuvant mixture was able to outperform fully conjugated vaccine compounds in antibody titre induction and in vitro opsonisation.

Adjuvants capable of inducing strong immune responses to co-administered antigens, without chemical conjugation, present several benefits over systems requiring conjugation. For example, lower risk of damaging peptide secondary structure, ability to optimise adjuvant / antigen ratio, potential to be used across a wide range of antigens and reducing the complexity of manufacturing.

Here, we focused on group a Streptococcus (GAS) as a model organism, with no vaccine currently approved. Invasive GAS infection causes numerous deleterious health effects, including the potentially fatal post infectious complications rheumatic fever and rheumatic heart disease. These post infectious complications are responsible for the largest proportion of the over 320,000 GAS related deaths worldwide per year.

We investigated three peptide-based building blocks, the conserved GAS B-cell antigen and universal T-helper epitope J8-PADRE, a known toll-like receptor 2 ligand C16 lipoamino acid, and a cyclic decapeptide carrier. These vaccine building blocks were synthesised and conjugated using standard solid phase peptide chemistry, copper catalysed click reactions and orthogonal protecting strategies. These compounds were then physically mixed to afford several vaccine candidates which were capable of inducing strong opsonic immune responses following in vivo immunological assessment. This nanoparticle adjuvant has the potential to facilitate the future development effective peptide-based subunit vaccines.

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  4. Madge, H. Y. R.; Huang, W.; Gilmartin, L.; Rigau-Planella, B.; Hussein, W. M.; Khalil, Z. G.; Koirala, P.; Santiago, V.; Capon, R.; Toth, I.; Stephenson, R. J., Physical mixture of a cyclic lipopeptide vaccine induced high titres of opsonic IgG antibodies against group a streptococcus. Biomaterials Science 2021, 10, 281-293.