Poster Presentation 8th Australasian Vaccines & Immunotherapeutics Development Meeting 2020

Development of Lipopeptide-based Adjuvants as Vaccine Candidates against Group A Streptococcus (GAS) (#104)

Farrhana Firdaus 1 , Jieru Yang 1 , Armira Azuar 1 , Mariusz Skwarczynski 1 , Istvan Toth 1 2 3
  1. 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

Vaccination is the most efficient medical invention to counter the effects of infectious diseases to date. Overtime, vaccine designs have evolved into more precisely defined formulations wuth antigens. Peptide-based subunit vaccines utilises selected microbial fragments which can eliminate adverse effects related issues associated with conventional vaccines [1]. However, peptide epitopes are known to be poor immunogens and would require the use of an adjuvant to enhance vaccine immunogenicity [2]. The addition of lipid moieties to the epitopes can improve the efficacy of peptide-based vaccines [3]. The main objective of the study was to evaluate and optimise the ability of lipopeptides (lipid-core peptides, antimicrobial peptides and short cationic peptides) to trigger immune response against the chosen antigens (J8, B-cell epitope derived from Group A Streptococcus (GAS) and universal T helper (P25)). The vaccine candidates was analysed as a mixture (physical mixture of lipopeptide and antigens) and conjugated construct (antigens conjugated to lipopeptide).  A series of potential lipopeptide-based adjuvants, conjugated construct and antigens were synthesised through solid phase peptide synthesis and analysed with mass spectrometry and reverse phase high performance liquid chromatography. Vaccine candidates were characterized with dynamic light scattering and circular dichroism. Additionally, enzyme-linked immunosorbent assay was used to detect and quantify J8-specific IgG titers collected from immunological studies performed in mice. Through the characterisation of the compounds, it was discovered that the particle size of the mixture was more stable and homogenous, suggesting the formation of complexes. Additionally, the secondary structure of the mixture was found to be a combination of α-helical and random coil similar to the conjugated construct. In vivo assessment of the vaccine candidates showed the conjugated construct was more effective. Except, one mixture (counterpart to the conjugated construct consisting of lipid-core peptides) was able to induce higher J8-specific IgG antibodies than the conjugated construct.  We were able to identify one lipopeptide with promising adjuvanting abilities which elicited higher IgG titers against the antigen while conjugated and in a mixture with the antigen in comparison to the other lipopeptides.

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  2. Coffman RL, Sher A, Seder RA: Vaccine adjuvants: putting innate immunity to work. Immunity 2010, 33(4):492-503.
  3. Bartlett S, Skwarczynski M, Toth I: Lipids as activators of innate immunity in peptide vaccine delivery. Current medicinal chemistry 2020, 27(17):2887-2901.