TY - JOUR
T1 - A dual-adjuvanting strategy for peptide-based subunit vaccines against group A Streptococcus
T2 - Lipidation and polyelectrolyte complexes
AU - Zhao, Lili
AU - Yang, Jieru
AU - Nahar, Ummey Jannatun
AU - Khalil, Zeinab G.
AU - Capon, Robert J.
AU - Hussein, Waleed M.
AU - Skwarczynski, Mariusz
AU - Toth, Istvan
N1 - Publisher Copyright:
© 2020 Elsevier Ltd
PY - 2020/12/15
Y1 - 2020/12/15
N2 - 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.
AB - 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.
KW - Cholic acid
KW - Intranasal immunization
KW - Lipopeptide
KW - Polyelectrolyte complexes
KW - Polyglutamic acid
KW - Trimethyl chitosan
UR - https://www.scopus.com/pages/publications/85093964294
U2 - 10.1016/j.bmc.2020.115823
DO - 10.1016/j.bmc.2020.115823
M3 - Article
C2 - 33120079
AN - SCOPUS:85093964294
SN - 0968-0896
VL - 28
JO - Bioorganic & Medicinal Chemistry
JF - Bioorganic & Medicinal Chemistry
IS - 24
M1 - 115823
ER -
