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West Ashley Library
9 a.m. – 7 p.m.
Phone: (843) 766-6635
Main Library
9 a.m. - 8 p.m.
Phone: (843) 805-6930
Folly Beach Library
Closed for renovations
Phone: (843) 588-2001
John L. Dart Library
9 a.m. – 7 p.m.
Phone: (843) 722-7550
St. Paul's/Hollywood Library
9 a.m. - 8 p.m.
Phone: (843) 889-3300
Mt. Pleasant Library
9 a.m. – 8 p.m.
Phone: (843) 849-6161
Dorchester Road Library
9 a.m. - 8 p.m.
Phone: (843) 552-6466
Edgar Allan Poe/Sullivan's Island Library
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John's Island Library
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McClellanville Library
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Edisto Library
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Wando Mount Pleasant Library
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Otranto Road Library
9 a.m. - 8 p.m.
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Phone: (843) 805-6892
Village Library
9 a.m. - 6 p.m.
Phone: (843) 884-9741
Keith Summey North Charleston Library
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Phone: (843) 805-6909
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Star nanoparticles delivering HIV-1 peptide minimal immunogens elicit near-native envelope antibody responses in nonhuman primates.
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- Author(s): Francica, Joseph R.; Laga, Richard; Lynn, Geoffrey M.; Mužíková, Gabriela; Androvič, Ladislav; Aussedat, Baptiste; Walkowicz, William E.; Padhan, Kartika; Ramirez-Valdez, Ramiro Andrei; Parks, Robert; Schmidt, Stephen D.; Flynn, Barbara J.; Tsybovsky, Yaroslav; Stewart-Jones, Guillaume B. E.; Saunders, Kevin O.; Baharom, Faezzah; Petrovas, Constantinos; Haynes, Barton F.; Seder, Robert A.
- Source:
PLoS Biology; 6/17/2019, Vol. 17 Issue 6, p1-28, 28p, 6 Graphs - Source:
- Additional Information
- Abstract: Peptide immunogens provide an approach to focus antibody responses to specific neutralizing sites on the HIV envelope protein (Env) trimer or on other pathogens. However, the physical characteristics of peptide immunogens can limit their pharmacokinetic and immunological properties. Here, we have designed synthetic “star” nanoparticles based on biocompatible N-[(2-hydroxypropyl)methacrylamide] (HPMA)-based polymer arms extending from a poly(amidoamine) (PAMAM) dendrimer core. In mice, these star nanoparticles trafficked to lymph nodes (LNs) by 4 hours following vaccination, where they were taken up by subcapsular macrophages and then resident dendritic cells (DCs). Immunogenicity optimization studies revealed a correlation of immunogen density with antibody titers. Furthermore, the co-delivery of Env variable loop 3 (V3) and T-helper peptides induced titers that were 2 logs higher than if the peptides were given in separate nanoparticles. Finally, we performed a nonhuman primate (NHP) study using a V3 glycopeptide minimal immunogen that was structurally optimized to be recognized by Env V3/glycan broadly neutralizing antibodies (bnAbs). When administered with a potent Toll-like receptor (TLR) 7/8 agonist adjuvant, these nanoparticles elicited high antibody binding titers to the V3 site. Similar to human V3/glycan bnAbs, certain monoclonal antibodies (mAbs) elicited by this vaccine were glycan dependent or targeted the GDIR peptide motif. To improve affinity to native Env trimer affinity, nonhuman primates (NHPs) were boosted with various SOSIP Env proteins; however, significant neutralization was not observed. Taken together, this study provides a new vaccine platform for administration of glycopeptide immunogens for focusing immune responses to specific bnAb epitopes. [ABSTRACT FROM AUTHOR]
- Abstract: Copyright of PLoS Biology is the property of Public Library of Science and its content may not be copied or emailed to multiple sites or posted to a listserv without the copyright holder's express written permission. However, users may print, download, or email articles for individual use. This abstract may be abridged. No warranty is given about the accuracy of the copy. Users should refer to the original published version of the material for the full abstract. (Copyright applies to all Abstracts.)
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