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

• Published in: Bioorganic & medicinal chemistry Vol. 28; no. 24; p. 115823
• Main Authors: Zhao, Lili, Yang, Jieru, Nahar, Ummey Jannatun, Khalil, Zeinab G., Capon, Robert J., Hussein, Waleed M., Skwarczynski, Mariusz, Toth, Istvan
• Format: Journal Article
• Language: English
• Published: England Elsevier Ltd 15.12.2020
• Subjects: Cholic acid; Intranasal immunization; Lipopeptide; Polyelectrolyte complexes; Polyglutamic acid; Trimethyl chitosan; Intranasal immunization; Cholic acid; Polyglutamic acid; Polyelectrolyte complexes; Lipopeptide; Trimethyl chitosan
• ISSN: 0968-0896; 1464-3391
• DOI: 10.1016/j.bmc.2020.115823

[Display omitted] 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.