-
Something wrong with this record ?
Star nanoparticles delivering HIV-1 peptide minimal immunogens elicit near-native envelope antibody responses in nonhuman primates
JR. Francica, R. Laga, GM. Lynn, G. Mužíková, L. Androvič, B. Aussedat, WE. Walkowicz, K. Padhan, RA. Ramirez-Valdez, R. Parks, SD. Schmidt, BJ. Flynn, Y. Tsybovsky, GBE. Stewart-Jones, KO. Saunders, F. Baharom, C. Petrovas, BF. Haynes, RA. Seder,
Language English Country United States
Document type Journal Article, Research Support, N.I.H., Intramural, Research Support, Non-U.S. Gov't
Grant support
UM1 AI100645
NIAID NIH HHS - United States
NLK
Directory of Open Access Journals
from 2003
Free Medical Journals
from 2003
Public Library of Science (PLoS)
from 2003
PubMed Central
from 2003
Europe PubMed Central
from 2003
ProQuest Central
from 2003-10-01
Open Access Digital Library
from 2003-10-01
Open Access Digital Library
from 2003-01-01
Open Access Digital Library
from 2003-01-01
Open Access Digital Library
from 2003-12-01
Medline Complete (EBSCOhost)
from 2003-10-01
Health & Medicine (ProQuest)
from 2003-10-01
- MeSH
- Epitopes immunology MeSH
- HIV Infections immunology MeSH
- HIV Envelope Protein gp120 chemistry MeSH
- HIV Seropositivity immunology MeSH
- HIV-1 immunology MeSH
- Macaca mulatta MeSH
- Mice, Inbred BALB C MeSH
- Mice MeSH
- Nanoparticles chemistry therapeutic use MeSH
- Antibodies, Neutralizing immunology MeSH
- Peptides MeSH
- Primates MeSH
- Antibody Formation immunology MeSH
- AIDS Vaccines immunology MeSH
- Animals MeSH
- Check Tag
- Mice MeSH
- Female MeSH
- Animals MeSH
- Publication type
- Journal Article MeSH
- Research Support, Non-U.S. Gov't MeSH
- Research Support, N.I.H., Intramural MeSH
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.
Avidea Technologies Inc Baltimore Maryland United States of America
Institute of Macromolecular Chemistry Czech Academy of Sciences Prague Czech Republic
References provided by Crossref.org
- 000
- 00000naa a2200000 a 4500
- 001
- bmc20006251
- 003
- CZ-PrNML
- 005
- 20200525153727.0
- 007
- ta
- 008
- 200511s2019 xxu f 000 0|eng||
- 009
- AR
- 024 7_
- $a 10.1371/journal.pbio.3000328 $2 doi
- 035 __
- $a (PubMed)31206510
- 040 __
- $a ABA008 $b cze $d ABA008 $e AACR2
- 041 0_
- $a eng
- 044 __
- $a xxu
- 100 1_
- $a Francica, Joseph R $u Vaccine Research Center, National Institute of Allergy and Infectious Diseases, National Institutes of Health, Bethesda, Maryland, United States of America.
- 245 10
- $a Star nanoparticles delivering HIV-1 peptide minimal immunogens elicit near-native envelope antibody responses in nonhuman primates / $c JR. Francica, R. Laga, GM. Lynn, G. Mužíková, L. Androvič, B. Aussedat, WE. Walkowicz, K. Padhan, RA. Ramirez-Valdez, R. Parks, SD. Schmidt, BJ. Flynn, Y. Tsybovsky, GBE. Stewart-Jones, KO. Saunders, F. Baharom, C. Petrovas, BF. Haynes, RA. Seder,
- 520 9_
- $a 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.
- 650 _2
- $a vakcíny proti AIDS $x imunologie $7 D016915
- 650 _2
- $a zvířata $7 D000818
- 650 _2
- $a neutralizující protilátky $x imunologie $7 D057134
- 650 _2
- $a tvorba protilátek $x imunologie $7 D000917
- 650 _2
- $a epitopy $x imunologie $7 D000939
- 650 _2
- $a ženské pohlaví $7 D005260
- 650 _2
- $a HIV obalový protein gp120 $x chemie $7 D015699
- 650 _2
- $a HIV infekce $x imunologie $7 D015658
- 650 _2
- $a HIV séropozitivita $x imunologie $7 D006679
- 650 _2
- $a HIV-1 $x imunologie $7 D015497
- 650 _2
- $a Macaca mulatta $7 D008253
- 650 _2
- $a myši $7 D051379
- 650 _2
- $a myši inbrední BALB C $7 D008807
- 650 _2
- $a nanočástice $x chemie $x terapeutické užití $7 D053758
- 650 _2
- $a peptidy $7 D010455
- 650 _2
- $a primáti $7 D011323
- 655 _2
- $a časopisecké články $7 D016428
- 655 _2
- $a Research Support, N.I.H., Intramural $7 D052060
- 655 _2
- $a práce podpořená grantem $7 D013485
- 700 1_
- $a Laga, Richard $u Institute of Macromolecular Chemistry, Czech Academy of Sciences, Prague, Czech Republic.
- 700 1_
- $a Lynn, Geoffrey M $u Avidea Technologies, Inc., Baltimore, Maryland, United States of America.
- 700 1_
- $a Mužíková, Gabriela $u Institute of Macromolecular Chemistry, Czech Academy of Sciences, Prague, Czech Republic.
- 700 1_
- $a Androvič, Ladislav $u Institute of Macromolecular Chemistry, Czech Academy of Sciences, Prague, Czech Republic.
- 700 1_
- $a Aussedat, Baptiste $u Department of Chemical Biology, Memorial Sloan Kettering Cancer Center, New York, New York, United States of America.
- 700 1_
- $a Walkowicz, William E $u Department of Chemical Biology, Memorial Sloan Kettering Cancer Center, New York, New York, United States of America.
- 700 1_
- $a Padhan, Kartika $u Vaccine Research Center, National Institute of Allergy and Infectious Diseases, National Institutes of Health, Bethesda, Maryland, United States of America.
- 700 1_
- $a Ramirez-Valdez, Ramiro Andrei $u Vaccine Research Center, National Institute of Allergy and Infectious Diseases, National Institutes of Health, Bethesda, Maryland, United States of America.
- 700 1_
- $a Parks, Robert $u Duke Human Vaccine Institute, Duke University School of Medicine, Durham, North Carolina, United States of America.
- 700 1_
- $a Schmidt, Stephen D $u Vaccine Research Center, National Institute of Allergy and Infectious Diseases, National Institutes of Health, Bethesda, Maryland, United States of America.
- 700 1_
- $a Flynn, Barbara J $u Vaccine Research Center, National Institute of Allergy and Infectious Diseases, National Institutes of Health, Bethesda, Maryland, United States of America.
- 700 1_
- $a Tsybovsky, Yaroslav $u Electron Microscopy Laboratory, Cancer Research Technology Program, Leidos Biomedical Research Inc., Frederick National Laboratory for Cancer Research, Frederick, Maryland, United States of America.
- 700 1_
- $a Stewart-Jones, Guillaume B E $u Vaccine Research Center, National Institute of Allergy and Infectious Diseases, National Institutes of Health, Bethesda, Maryland, United States of America.
- 700 1_
- $a Saunders, Kevin O $u Duke Human Vaccine Institute, Duke University School of Medicine, Durham, North Carolina, United States of America.
- 700 1_
- $a Baharom, Faezzah $u Vaccine Research Center, National Institute of Allergy and Infectious Diseases, National Institutes of Health, Bethesda, Maryland, United States of America.
- 700 1_
- $a Petrovas, Constantinos $u Vaccine Research Center, National Institute of Allergy and Infectious Diseases, National Institutes of Health, Bethesda, Maryland, United States of America.
- 700 1_
- $a Haynes, Barton F $u Duke Human Vaccine Institute, Duke University School of Medicine, Durham, North Carolina, United States of America.
- 700 1_
- $a Seder, Robert A $u Vaccine Research Center, National Institute of Allergy and Infectious Diseases, National Institutes of Health, Bethesda, Maryland, United States of America.
- 773 0_
- $w MED00008061 $t PLoS biology $x 1545-7885 $g Roč. 17, č. 6 (2019), s. e3000328
- 856 41
- $u https://pubmed.ncbi.nlm.nih.gov/31206510 $y Pubmed
- 910 __
- $a ABA008 $b sig $c sign $y a $z 0
- 990 __
- $a 20200511 $b ABA008
- 991 __
- $a 20200525153727 $b ABA008
- 999 __
- $a ok $b bmc $g 1525109 $s 1096307
- BAS __
- $a 3
- BAS __
- $a PreBMC
- BMC __
- $a 2019 $b 17 $c 6 $d e3000328 $e 20190617 $i 1545-7885 $m PLoS biology $n Plos Biol $x MED00008061
- GRA __
- $a UM1 AI100645 $p NIAID NIH HHS $2 United States
- LZP __
- $a Pubmed-20200511