dc.contributor.author | Nevagi, Reshma J | |
dc.contributor.author | Dai, Wei | |
dc.contributor.author | Khalil, Zeinab G | |
dc.contributor.author | Hussein, Waleed M | |
dc.contributor.author | Capon, Robert J | |
dc.contributor.author | Skwarczynski, Mariusz | |
dc.contributor.author | Toth, Istvan | |
dc.date.accessioned | 2020-05-18T03:50:35Z | |
dc.date.available | 2020-05-18T03:50:35Z | |
dc.date.issued | 2019 | |
dc.identifier.issn | 0223-5234 | |
dc.identifier.doi | 10.1016/j.ejmech.2019.06.047 | |
dc.identifier.uri | http://hdl.handle.net/10072/393934 | |
dc.description.abstract | Synthetic 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.description.peerreviewed | Yes | |
dc.language | English | |
dc.language.iso | eng | |
dc.publisher | Elsevier | |
dc.relation.ispartofpagefrom | 100 | |
dc.relation.ispartofpageto | 108 | |
dc.relation.ispartofjournal | European Journal of Medicinal Chemistry | |
dc.relation.ispartofvolume | 179 | |
dc.subject.fieldofresearch | Medicinal and biomolecular chemistry | |
dc.subject.fieldofresearch | Organic chemistry | |
dc.subject.fieldofresearch | Pharmacology and pharmaceutical sciences | |
dc.subject.fieldofresearchcode | 3404 | |
dc.subject.fieldofresearchcode | 3405 | |
dc.subject.fieldofresearchcode | 3214 | |
dc.title | Structure-activity relationship of group A streptococcus lipopeptide vaccine candidates in trimethyl chitosan-based self-adjuvanting delivery system | |
dc.type | Journal article | |
dc.type.description | C1 - Articles | |
dcterms.bibliographicCitation | Nevagi, 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 | |
dc.date.updated | 2020-05-18T03:48:51Z | |
gro.hasfulltext | No Full Text | |
gro.griffith.author | Nevagi, Reshma J. | |