-
Je něco špatně v tomto záznamu ?
Impact of Polymer-TLR-7/8 Agonist (Adjuvant) Morphology on the Potency and Mechanism of CD8 T Cell Induction
GM. Lynn, P. Chytil, JR. Francica, A. Lagová, G. Kueberuwa, AS. Ishizuka, N. Zaidi, RA. Ramirez-Valdez, NJ. Blobel, F. Baharom, J. Leal, AQ. Wang, MY. Gerner, T. Etrych, K. Ulbrich, LW. Seymour, RA. Seder, R. Laga,
Jazyk angličtina Země Spojené státy americké
Typ dokumentu časopisecké články, Research Support, N.I.H., Intramural, práce podpořená grantem
- MeSH
- adjuvancia imunologická aplikace a dávkování chemie farmakologie MeSH
- aktivace lymfocytů * MeSH
- buněčné linie MeSH
- CD8-pozitivní T-lymfocyty účinky léků imunologie MeSH
- cytokiny metabolismus MeSH
- hydrodynamika MeSH
- kultivované buňky MeSH
- micely * MeSH
- myši inbrední C57BL MeSH
- myši MeSH
- toll-like receptor 7 agonisté MeSH
- toll-like receptor 8 agonisté MeSH
- vazba proteinů MeSH
- zvířata MeSH
- Check Tag
- myši MeSH
- ženské pohlaví MeSH
- zvířata MeSH
- Publikační typ
- časopisecké články MeSH
- práce podpořená grantem MeSH
- Research Support, N.I.H., Intramural MeSH
Small molecule Toll-like receptor-7 and -8 agonists (TLR-7/8a) can be used as vaccine adjuvants to induce CD8 T cell immunity but require formulations that prevent systemic toxicity and focus adjuvant activity in lymphoid tissues. Here, we covalently attached TLR-7/8a to polymers of varying composition, chain architecture and hydrodynamic behavior (∼300 nm submicrometer particles, ∼10 nm micelles and ∼4 nm flexible random coils) and evaluated how these parameters of polymer-TLR-7/8a conjugates impact adjuvant activity in vivo. Attachment of TLR-7/8a to any of the polymer compositions resulted in a nearly 10-fold reduction in systemic cytokines (toxicity). Moreover, both lymph node cytokine production and the magnitude of CD8 T cells induced against protein antigen increased with increasing polymer-TLR-7/8a hydrodynamic radius, with the submicrometer particle inducing the highest magnitude responses. Notably, CD8 T cell responses induced by polymer-TLR-7/8a were dependent on CCR2+ monocytes and IL-12, whereas responses by a small molecule TLR-7/8a that unexpectedly persisted in vaccine-site draining lymph nodes (T1/2 = 15 h) had less dependence on monocytes and IL-12 but required Type I IFNs. This study shows how modular properties of synthetic adjuvants can be chemically programmed to alter immunity in vivo through distinct immunological mechanisms.
Citace poskytuje Crossref.org
- 000
- 00000naa a2200000 a 4500
- 001
- bmc20006667
- 003
- CZ-PrNML
- 005
- 20200518132857.0
- 007
- ta
- 008
- 200511s2019 xxu f 000 0|eng||
- 009
- AR
- 024 7_
- $a 10.1021/acs.biomac.8b01473 $2 doi
- 035 __
- $a (PubMed)30608149
- 040 __
- $a ABA008 $b cze $d ABA008 $e AACR2
- 041 0_
- $a eng
- 044 __
- $a xxu
- 100 1_
- $a Lynn, Geoffrey M $u Vaccine Research Center, National Institute of Allergy and Infectious Diseases , National Institutes of Health, 40 Convent Drive , Bethesda , Maryland 20892 , United States.
- 245 10
- $a Impact of Polymer-TLR-7/8 Agonist (Adjuvant) Morphology on the Potency and Mechanism of CD8 T Cell Induction / $c GM. Lynn, P. Chytil, JR. Francica, A. Lagová, G. Kueberuwa, AS. Ishizuka, N. Zaidi, RA. Ramirez-Valdez, NJ. Blobel, F. Baharom, J. Leal, AQ. Wang, MY. Gerner, T. Etrych, K. Ulbrich, LW. Seymour, RA. Seder, R. Laga,
- 520 9_
- $a Small molecule Toll-like receptor-7 and -8 agonists (TLR-7/8a) can be used as vaccine adjuvants to induce CD8 T cell immunity but require formulations that prevent systemic toxicity and focus adjuvant activity in lymphoid tissues. Here, we covalently attached TLR-7/8a to polymers of varying composition, chain architecture and hydrodynamic behavior (∼300 nm submicrometer particles, ∼10 nm micelles and ∼4 nm flexible random coils) and evaluated how these parameters of polymer-TLR-7/8a conjugates impact adjuvant activity in vivo. Attachment of TLR-7/8a to any of the polymer compositions resulted in a nearly 10-fold reduction in systemic cytokines (toxicity). Moreover, both lymph node cytokine production and the magnitude of CD8 T cells induced against protein antigen increased with increasing polymer-TLR-7/8a hydrodynamic radius, with the submicrometer particle inducing the highest magnitude responses. Notably, CD8 T cell responses induced by polymer-TLR-7/8a were dependent on CCR2+ monocytes and IL-12, whereas responses by a small molecule TLR-7/8a that unexpectedly persisted in vaccine-site draining lymph nodes (T1/2 = 15 h) had less dependence on monocytes and IL-12 but required Type I IFNs. This study shows how modular properties of synthetic adjuvants can be chemically programmed to alter immunity in vivo through distinct immunological mechanisms.
- 650 _2
- $a adjuvancia imunologická $x aplikace a dávkování $x chemie $x farmakologie $7 D000276
- 650 _2
- $a zvířata $7 D000818
- 650 _2
- $a CD8-pozitivní T-lymfocyty $x účinky léků $x imunologie $7 D018414
- 650 _2
- $a buněčné linie $7 D002460
- 650 _2
- $a kultivované buňky $7 D002478
- 650 _2
- $a cytokiny $x metabolismus $7 D016207
- 650 _2
- $a ženské pohlaví $7 D005260
- 650 _2
- $a hydrodynamika $7 D057446
- 650 12
- $a aktivace lymfocytů $7 D008213
- 650 _2
- $a myši $7 D051379
- 650 _2
- $a myši inbrední C57BL $7 D008810
- 650 12
- $a micely $7 D008823
- 650 _2
- $a vazba proteinů $7 D011485
- 650 _2
- $a toll-like receptor 7 $x agonisté $7 D051199
- 650 _2
- $a toll-like receptor 8 $x agonisté $7 D051200
- 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 Chytil, Petr $u Institute of Macromolecular Chemistry, Czech Academy of Sciences , Heyrovského nám. 2 , 162 06 Prague 6 , Czech Republic.
- 700 1_
- $a Francica, Joseph R $u Vaccine Research Center, National Institute of Allergy and Infectious Diseases , National Institutes of Health, 40 Convent Drive , Bethesda , Maryland 20892 , United States.
- 700 1_
- $a Lagová, Anna $u Department of Oncology , University of Oxford , Old Road Campus Research Building , Oxford OX3 7DQ , United Kingdom.
- 700 1_
- $a Kueberuwa, Gray $u Department of Oncology , University of Oxford , Old Road Campus Research Building , Oxford OX3 7DQ , United Kingdom.
- 700 1_
- $a Ishizuka, Andrew S $u Vaccine Research Center, National Institute of Allergy and Infectious Diseases , National Institutes of Health, 40 Convent Drive , Bethesda , Maryland 20892 , United States.
- 700 1_
- $a Zaidi, Neeha $u Vaccine Research Center, National Institute of Allergy and Infectious Diseases , National Institutes of Health, 40 Convent Drive , Bethesda , Maryland 20892 , United States.
- 700 1_
- $a Ramirez-Valdez, Ramiro A $u Vaccine Research Center, National Institute of Allergy and Infectious Diseases , National Institutes of Health, 40 Convent Drive , Bethesda , Maryland 20892 , United States.
- 700 1_
- $a Blobel, Nicolas J $u Vaccine Research Center, National Institute of Allergy and Infectious Diseases , National Institutes of Health, 40 Convent Drive , Bethesda , Maryland 20892 , United States.
- 700 1_
- $a Baharom, Faezzah $u Vaccine Research Center, National Institute of Allergy and Infectious Diseases , National Institutes of Health, 40 Convent Drive , Bethesda , Maryland 20892 , United States.
- 700 1_
- $a Leal, Joseph $u Department of Immunology , University of Washington , South Lake Union E-411, 750 Republican Street , Seattle , Washington 98109 , United States.
- 700 1_
- $a Wang, Amy Q $u Therapeutics for Rare and Neglected Diseases, National Center for Advancing Translational Sciences , 9800 Medical Center Drive , Rockville , Maryland 20850 , United States.
- 700 1_
- $a Gerner, Michael Y $u Department of Immunology , University of Washington , South Lake Union E-411, 750 Republican Street , Seattle , Washington 98109 , United States.
- 700 1_
- $a Etrych, Tomáš $u Institute of Macromolecular Chemistry, Czech Academy of Sciences , Heyrovského nám. 2 , 162 06 Prague 6 , Czech Republic.
- 700 1_
- $a Ulbrich, Karel $u Institute of Macromolecular Chemistry, Czech Academy of Sciences , Heyrovského nám. 2 , 162 06 Prague 6 , Czech Republic.
- 700 1_
- $a Seymour, Leonard W $u Department of Oncology , University of Oxford , Old Road Campus Research Building , Oxford OX3 7DQ , United Kingdom.
- 700 1_
- $a Seder, Robert A $u Vaccine Research Center, National Institute of Allergy and Infectious Diseases , National Institutes of Health, 40 Convent Drive , Bethesda , Maryland 20892 , United States.
- 700 1_
- $a Laga, Richard $u Institute of Macromolecular Chemistry, Czech Academy of Sciences , Heyrovského nám. 2 , 162 06 Prague 6 , Czech Republic. Department of Oncology , University of Oxford , Old Road Campus Research Building , Oxford OX3 7DQ , United Kingdom.
- 773 0_
- $w MED00006456 $t Biomacromolecules $x 1526-4602 $g Roč. 20, č. 2 (2019), s. 854-870
- 856 41
- $u https://pubmed.ncbi.nlm.nih.gov/30608149 $y Pubmed
- 910 __
- $a ABA008 $b sig $c sign $y a $z 0
- 990 __
- $a 20200511 $b ABA008
- 991 __
- $a 20200518132857 $b ABA008
- 999 __
- $a ok $b bmc $g 1525525 $s 1096723
- BAS __
- $a 3
- BAS __
- $a PreBMC
- BMC __
- $a 2019 $b 20 $c 2 $d 854-870 $e 20190122 $i 1526-4602 $m Biomacromolecules $n Biomacromolecules $x MED00006456
- LZP __
- $a Pubmed-20200511
