title: Structure-activity relationship of a series of synthetic lipopeptide self-adjuvanting group a streptococcal vaccine candidates.
abstract: The development of 16 self-adjuvanting group A streptococcal vaccine candidates, composed of (i) a universal helper T-cell epitope (P25), (ii) a target GAS B-cell epitope (J14), and (iii) a lipid moiety, is described. Systemic J14-specific IgG antibodies were detected following subcutaneous immunization of BALB/c (H-2 (d)) mice with each construct without the need for an additional adjuvant. The effect of changing the order of P25, J14, and lipid moiety attachment or incorporation of P25 and J14 into a lipid-core peptide system on antibody titers was assessed. The point of lipid moiety attachment had the greatest influence on systemic J14-specific IgG antibody titers. Overall, the best vaccines featured a C-terminal lipid moiety, conjugated through a lysine residue to P25 at the N-terminus, and J14 on the lysine side chain.
authors: School of Molecular and Microbial Sciences, The University of Queensland, St. Lucia 4072, Queensland, Australia.
authors: Abu-Baker M
authors: AB
authors: Abdel-Aal
authors: Michael R
authors: MR
authors: Batzloff
authors: Yoshio
authors: Y
authors: Fujita
authors: Nadia
authors: N
authors: Barozzi
authors: Andres
authors: A
authors: Faria
authors: Pavla
authors: P
authors: Simerska
authors: Peter M
authors: PM
authors: Moyle
authors: Michael F
authors: MF
authors: Good
authors: Istvan
authors: I
authors: Toth
mesh_terms: D000596:Amino Acids / Q000737:chemistry*; D000818:Animals; D018985:Epitopes, B-Lymphocyte; D018984:Epitopes, T-Lymphocyte; D005260:Female; D007074:Immunoglobulin G / Q000097:blood; D008055:Lipids / Q000737:chemistry*; D051379:Mice; D008807:Mice, Inbred BALB C; D022541:Streptococcal Vaccines / Q000138:chemical synthesis* / Q000276:immunology; D013297:Streptococcus pyogenes / Q000276:immunology*; D013329:Structure-Activity Relationship; D022223:Vaccines, Subunit / Q000138:chemical synthesis* / Q000276:immunology; D014614:Vaccines, Synthetic / Q000276:immunology
chemical_list: D000596:Amino Acids; D018985:Epitopes, B-Lymphocyte; D018984:Epitopes, T-Lymphocyte; D007074:Immunoglobulin G; D008055:Lipids; D022541:Streptococcal Vaccines; D022223:Vaccines, Subunit; D014614:Vaccines, Synthetic