Poster Presentation Asia-Pacific Vaccine and Immunotherapy Congress 2023

Poly(hydrophobic amino acids) as an adjuvant for subunit vaccines (#108)

Lantian Lu 1 , Mariusz Skwarczynski 1 , Istvan Toth 1 2 3
  1. School of Chemistry and Molecular Biosciences, The University of Queensland, Brisbane, Queensland, Australia
  2. Institute of Molecular Bioscience, The University of Queensland, Brisbane, Queensland, Australia
  3. School of Pharmacy, The University of Queensland, Brisbane, Queensland, Australia

Peptide-based adjuvants are promising tools for enhancing immune responses to peptide or protein antigens. Poly(hydrophobic amino acids) (pHAA) have previously demonstrated good adjuvanticity when conjugated to a peptide antigen to form nanovaccines [1-3]. However, pHAA required conjugation to the antigen to induce desired immune responses, which significantly increases the complexity of produced vaccine. Here we propose that pHAA when physically mixed with an antigen can also enhance the immunogenicity of the antigen, reducing the cost and simplifying the manufacturing process.

 

In this study, polyleucine derivatives containing 15 leucine residues with solubilizing moieties of different charges (positive, neutral, and negative) were synthesized and found to self-assemble into nano-scale particles in an aqueous solution. When admixed with a peptide antigen, the polyleucine derivative with a positively charged solubilizing moiety, outperformed its neutral and negative counterparts in inducing the production of IgG antibodies against the peptide antigen. Moreover, positively charged pHAA in a mixture with antigen showed superior dendritic cell activation. To further evaluate the potential of positively charged pHAA it was then co-delivered with a model protein antigen, bovine serum albumin (BSA), in mice. The positively charged pHAA managed to outperform the commercialized adjuvant alum in helping generate BSA-specific IgG antibodies.

 

Overall, these findings highlight the potential of positively charged pHAA as a peptide-based adjuvant for enhancing immune responses against peptide or protein antigens.

 

  1. Skwarczynski, M. et al. Poly(amino acids) as a potent self-adjuvanting delivery system for peptide-based nanovaccines. Sci Adv 6, eaax2285, doi:10.1126/sciadv.aax2285 (2020).
  2. Shalash, A. O. et al. Oral Peptide Vaccine against Hookworm Infection: Correlation of Antibody Titers with Protective Efficacy. Vaccines (Basel) 9, doi:10.3390/vaccines9091034 (2021).
  3. Firdaus, F. Z. et al. Liposomal Formulations of a Polyleucine-Antigen Conjugate as Therapeutic Vaccines against Cervical Cancer. Pharmaceutics 15, 602 (2023).