Poster Presentation Asia-Pacific Vaccine and Immunotherapy Congress 2023

Development of cyclic lipopeptide-based vaccine candidates against group A Streptococcus (#156)

Jiahui Zhang 1 , Wenbin Huang 1 , Asmaa Mahmoud 1 , Harrison YR Madge 2 , Waleed M Hussein 2 , 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 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

INTRODUCTION

Group A Streptococcus (GAS) is a highly pathogenic bacterium that causes infections ranging from mild symptoms to life-threatening conditions, like rheumatic heart disease.1 We investigated the potential of a cyclic lipopeptide delivery system as a universal vehicle for presenting peptide antigens against GAS.2,3 In this study, we assessed the structure-immunogenicity relationship of a universal T helper epitope conjugated at the C- or N-terminus to three different GAS B cell epitopes in a mouse model and observed the importance of antigen orientation in vaccine design.

METHODS

All peptide moieties were synthesised via solid-phase peptide synthesis and characterised by liquid chromatography and mass spectrometry. In vitro, we analysed the secondary structure of the vaccine building blocks. Also, the particles were characterised utilising dynamic light scattering and transmission electron microscopy. In vivo, female C57BL/6 mice were immunised subcutaneously four times prior to determining the antigen-specific total immunoglobulin G (IgG) antibodies by ELISA and estimating the percentage of opsonic antibodies against different GAS clinical isolates.

RESULTS AND DISCUSSION

All vaccine candidates induced high antigen-specific systemic IgG titers and high opsonic potential compared with the antigen co-administered with a commercial adjuvant (complete Freund’s adjuvant). Interestingly, the 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 physicochemical assay.

CONCLUSION

We investigated cyclic lipopeptide as a vaccine delivery strategy for a variety of GAS epitope replacements, as well as orientation shifts with T helper epitope. The 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.

REFERENCES

  1. Castro SA, Dorfmueller HC. R Soc Open Sci. 2021 (8(3)) 201991.
  2. Madge HYR, Sharma H, Hussein WM, et al. J Med Chem. 2020 (63(10)) 5387-5397.
  3. Huang W, Madge HYR, Zhang J, et al. Int J Pharm. 2022 (617) 121614.