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dc.contributor.authorNevagi, Reshma J
dc.contributor.authorDai, Wei
dc.contributor.authorKhalil, Zeinab G
dc.contributor.authorHussein, Waleed M
dc.contributor.authorCapon, Robert J
dc.contributor.authorSkwarczynski, Mariusz
dc.contributor.authorToth, Istvan
dc.description.abstractSynthetic peptide vaccines based on epitopes derived from the conserved region of M-protein are proving to be a realistic option for protection against group A streptococcus (GAS). However, peptide epitopes alone are poorly immunogenic due to lack of pathogen-associated structural patterns. Therefore, we developed a GAS peptide vaccine based on combined lipidic TLR 2 agonist and self-adjuvanting polymers. We synthesized three α-poly-l-glutamic acid (PGA) conjugated lipopeptides composed of 2-amino-d,l-hexadecanoic acid, GAS B-cell peptide epitope J8 (QAEDKVKQSREAKKQVEKALKQLEDKVQ) and universal T-helper epitope PADRE (AKFVAAWTLKAAA) in different spatial arrangements. The anionic lipopeptide conjugates formed nanoparticles via ionic-complexation with a cationic polymer, trimethyl chitosan (TMC). We demonstrated that the spatial arrangement of vaccine components has a significant influence on peptide conformation and particle formation and, as such, contributes to the differential efficacy and opsonin-mediated killing potential of nanovaccines. Nanoparticles carrying branched helical lipopeptide with T-helper epitope on free N-termini (NP3) stimulated the most potent humoral immune responses. Lipopeptides without TMC (LP1-LP3) and TMC nanoparticles of peptide alone (without lipid) NP (P1) were poor inducers of antibody production, indicating that both TMC and lipid are required to induce a strong opsonic immune response.
dc.relation.ispartofjournalEuropean Journal of Medicinal Chemistry
dc.subject.fieldofresearchMedicinal and Biomolecular Chemistry
dc.subject.fieldofresearchOrganic Chemistry
dc.subject.fieldofresearchPharmacology and Pharmaceutical Sciences
dc.titleStructure-activity relationship of group A streptococcus lipopeptide vaccine candidates in trimethyl chitosan-based self-adjuvanting delivery system
dc.typeJournal article
dc.type.descriptionC1 - Articles
dcterms.bibliographicCitationNevagi, RJ; Dai, W; Khalil, ZG; Hussein, WM; Capon, RJ; Skwarczynski, M; Toth, I, Structure-activity relationship of group A streptococcus lipopeptide vaccine candidates in trimethyl chitosan-based self-adjuvanting delivery system, European Journal of Medicinal Chemistry, 2019, 179, pp. 100-108
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gro.griffith.authorNevagi, Reshma J.

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