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

Lili Zhao; Jieru Yang; Ummey Jannatun Nahar; Zeinab G Khalil; Robert J Capon; Waleed M Hussein; Mariusz Skwarczynski; Istvan Toth

doi:10.1016/j.bmc.2020.115823

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

Bioorg Med Chem. 2020 Dec 15;28(24):115823. doi: 10.1016/j.bmc.2020.115823. Epub 2020 Oct 20.

Authors

Lili Zhao¹, Jieru Yang¹, Ummey Jannatun Nahar¹, Zeinab G Khalil², Robert J Capon², Waleed M Hussein³, Mariusz Skwarczynski⁴, Istvan Toth⁵

Affiliations

¹ School of Chemistry & Molecular Biosciences, The University of Queensland, St Lucia, QLD 4072, Australia.
² Institute for Molecular Bioscience, The University of Queensland, St. Lucia, QLD 4072, Australia.
³ School of Chemistry & Molecular Biosciences, The University of Queensland, St Lucia, QLD 4072, Australia; Pharmaceutical Organic Chemistry Department, Faculty of Pharmacy, Helwan University, Helwan 11795, Egypt.
⁴ School of Chemistry & Molecular Biosciences, The University of Queensland, St Lucia, QLD 4072, Australia. Electronic address: m.skwarczynski@uq.edu.au.
⁵ School of Chemistry & Molecular Biosciences, The University of Queensland, St Lucia, QLD 4072, Australia; Institute for Molecular Bioscience, The University of Queensland, St. Lucia, QLD 4072, Australia; School of Pharmacy, The University of Queensland, Woolloongabba, QLD 4102, Australia. Electronic address: i.toth@uq.edu.au.

PMID: 33120079
DOI: 10.1016/j.bmc.2020.115823

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.

Publication types

Research Support, Non-U.S. Gov't

MeSH terms

Adjuvants, Immunologic
Administration, Intranasal
Animals
Antibodies / immunology
Cell Line
Cell Survival / drug effects
Chitosan / chemistry
Chromobox Protein Homolog 5
Female
Humans
Immunity, Humoral
Lipopeptides / administration & dosage
Lipopeptides / chemistry
Lipopeptides / immunology*
Lipopeptides / pharmacology
Mice
Nanoparticles / chemistry
Polyelectrolytes / chemistry
Polyglutamic Acid / chemistry
Streptococcal Infections / microbiology
Streptococcal Infections / prevention & control
Streptococcus pyogenes / immunology*
Vaccines, Subunit / administration & dosage
Vaccines, Subunit / chemistry
Vaccines, Subunit / immunology*
Vaccines, Subunit / pharmacology

Substances

Adjuvants, Immunologic
Antibodies
CBX5 protein, human
Lipopeptides
Polyelectrolytes
Vaccines, Subunit
Chromobox Protein Homolog 5
Polyglutamic Acid
Chitosan