Detail
Článek
Článek online
FT
Medvik - BMČ
  • Je něco špatně v tomto záznamu ?

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,

. 2019 ; 17 (6) : e3000328. [pub] 20190617

Jazyk angličtina Země Spojené státy americké

Typ dokumentu časopisecké články, Research Support, N.I.H., Intramural, práce podpořená grantem

Perzistentní odkaz   https://www.medvik.cz/link/bmc20006251

Grantová podpora
UM1 AI100645 NIAID NIH HHS - United States

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.

Citace poskytuje 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

Najít záznam

Citační ukazatele

Možnosti archivace