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A dual-adjuvanting strategy for peptide-based subunit vaccines against group A Streptococcus: Lipidation and

Lili Zhao¹, Jieru Yang¹, Ummey Jannatun Nahar¹

¹School of Chemistry & Molecular Biosciences, The University of Queensland, St Lucia, QLD 4072, Australia.

Bioorganic & Medicinal Chemistry

|October 29, 2020

Abstract:

In order to improve the immunogenicity of peptide-based vaccines against group A Streptococcus (GAS), lipid moieties (C16 lipoamino acid and cholic acid) were conjugated with peptide antigen (P25-J8) and further modified with α-poly(glutamic acid) (α-PGA). Thus, positively charged lipopeptide vaccine candidates LCP-1 (P25-K(J8)-SS-C16-C16) and LCP-2 (P25-K(J8)-SS-K(cholic acid)) were synthesized. Negatively charged LCP-3 (P25-K(PGA-J8)-SS-K(cholic acid)) was also produced by attaching α-PGA to the J8 N-terminus of LCP-2. Polyelectrolyte complex (PEC) nanoparticles were formulated with heparin and/or trimethyl chitosan (TMC) for delivery of the lipopeptide vaccine candidates. The ability of the antigen-loaded nanoparticles to induce humoral immune responses was examined in outbred female Swiss mice following intranasal immunization. The antibodies produced were opsonic against all clinical GAS isolates tested.

Keywords:

Cholic acid Intranasal immunization Lipopeptide Polyelectrolyte complexes Polyglutamic acid Trimethyl chitosan

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