Lipid Peptide Core Nanoparticles as Multivalent Vaccine Candidates against Streptococcus pyogenes

Abstract

Traditional vaccine approaches for Group A streptococcus (GAS) infection are inadequate owing to the host’s production of cross-reactive antibodies that recognize not only the bacteria but also human tissue. To overcome this problem a peptide subunit-based vaccine was proposed, which would incorporate only minimal non-cross reactive epitopes. However, special delivery systems/adjuvants were required because short peptides are not immunogenic. In this study we have incorporated two epitopes from two different GAS proteins into a lipid core peptide (LCP) self-adjuvanting delivery system to achieve better protection against a wide range of GAS serotypes. Multivalent and monovalent constructs were synthesized with the help of an azide alkyne cycloaddition (click) reaction and their ability to self-assemble under aqueous conditions was examined. The compounds significantly differed in their ability to form small size nanoparticles, which are believed to be most appropriate for peptide-based subunit vaccine delivery. The LCP conjugates possessing two different epitopes, in contrast to monoepitopic constructs, formed small nanoparticles (5–15 nm) presumably owing to a suitable hydrophilic-hydrophobic balance of the molecules.

Self-Adjuvanting Polymer–Peptide Conjugates As Therapeutic Vaccine Candidates against Cervical Cancer

“…21,[39][40][41] Analysis of the reaction showed that instead of the desired 'click' product 3, a disulfide bond-mediated dimer of 2 was exclusively produced.…”

pH-triggered peptide self-assembly into fibrils: a potential peptide-based subunit vaccine delivery platform

“…The conjugation was performed as previously described [27,28]. Briefly, compounds 3 (2.05 mg, 1.65 x 10 -3 mmol) and 7 (7.41 mg, 1.65 x 10 -3 mmol) were dissolved in DMF (1 mL) and copper wires were added (70 mg).…”

Lipid core peptide targeting the cathepsin D hemoglobinase ofSchistosoma mansonias a component of a schistosomiasis vaccine

“…The synthesis was performed in a similar manner to that previously reported. 15,19,48 Briefly, Boc-deprotection was performed with neat TFA (2 × 1 min), followed by a 1 min DMF flow wash. Boc-protected amino acids (4.2 equiv.) were pre-activated with 0.5 M HBTU/DMF solution (4.0 equiv.…”