Enhancing peptide-based vaccine immunogenicity: role of cyclic decapeptide as a multivalent scaffold — ASN Events
  1. Schedule
  2. Poster Session 2 - Wine Tasting
  3. Enhancing peptide-based vaccine immunogenicity: role of cyclic decapeptide as a multivalent scaffold

Enhancing peptide-based vaccine immunogenicity: role of cyclic decapeptide as a multivalent scaffold (#393)

Jiahui JZ Zhang 1 , Harrison HM Madge 2 , Wenbin WH Huang 1 , Asmaa AM Mahmoud 1 , Waleed WH Hussein 2 , Zeinab ZK Khalil 2 , Prashamsa PK Koirala 2 , Rob RC Capon 2 , Istvan IT Toth 1 2 3 , Rachel RS Stephenson 1
  1. School of Chemistry and Molecular Biosciences, The University of Queenslands, St Lucia, QLD, Australia
  2. Institute for Molecular Bioscience, The University of Queenslands, St Lucia, QLD, Australia
  3. School of Pharmacy, The University of Queenslands, St Lucia, QLD, Australia

Peptide-based vaccines universally suffer from a lack of immunogenicity unless they are delivered with immune stimulants or delivery systems.1 We investigated the cyclic decapeptide as a functionalizable scaffold for multivalently presenting peptide epitopes against group A Streptococcus (GAS).2,3,4 The multicomponent vaccine candidates consist of a cyclic decapeptide, a toll-like receptor 2-targeting lipid moiety, a pathogen-derived B cell epitope (J8, NS1 or 88/30) and a universal T helper epitope (PADRE). In this study, we assessed the structure-immunogenicity relationship between these components and observed the importance of antigen orientation in vaccine design.  All peptide moieties were synthesized by solid-phase peptide synthesis and characterized via liquid chromatography and mass spectrometry. The formation of peptide nanostructures was captured using transmission electron microscopy and dynamic light scattering. In vivo, C57BL/6 mice were immunized subcutaneously, and all vaccine candidates induced high levels of antigen-specific total immunoglobulin G (IgG) titers, as determined by ELISA. Furthermore, a high percentage of bactericidal antibodies against different GAS clinical isolates were observed compared to the antigen co-administered with a commercial adjuvant (complete Freund’s adjuvant). Interestingly, vaccines containing the GAS B-cell epitope exposed at the C-terminus of the T helper elicited stronger immunogenicity, and this corresponded to the alpha helix levels in the peptide secondary structure verified by the physicochemical assays. In summary, we investigated the adjuvanticity of cyclic lipopeptide by exploring various GAS epitope replacements as well as orientation shifts with T helper epitope. Our study revealed the importance of the free B cell epitope at the C-terminus of the T helper epitope, and the impact secondary structure plays on the immunogenicity of peptide-based vaccines. The physically mixed VC-13 emerged as the most efficient self-assembling vaccine candidate, demonstrating its potential to act as a universal adjuvant.

  1. 1. Skwarczynski M, Toth I. Chem Sci. 2016 (7(2)) 842-854. 2. Madge HYR, Sharma H, Hussein WM, et al. J Med Chem. 2020 (63(10)) 5387-5397. 3. Madge HYR, Huang W, Gilmartin L, et al. Biomater Sci. 2022,10,281. 4. Huang W, Madge HYR, Zhang J, et al. Int J Pharm. 2022 (617) 121614.
#AusPeptide2023