Impact of polymer-TLR-7/8 agonist (adjuvant) morphology on the potency and mechanism of CD8 T cell induction
The result's identifiers
Result code in IS VaVaI
<a href="https://www.isvavai.cz/riv?ss=detail&h=RIV%2F61389013%3A_____%2F19%3A00501308" target="_blank" >RIV/61389013:_____/19:00501308 - isvavai.cz</a>
Result on the web
<a href="https://pubs.acs.org/doi/10.1021/acs.biomac.8b01473" target="_blank" >https://pubs.acs.org/doi/10.1021/acs.biomac.8b01473</a>
DOI - Digital Object Identifier
<a href="http://dx.doi.org/10.1021/acs.biomac.8b01473" target="_blank" >10.1021/acs.biomac.8b01473</a>
Alternative languages
Result language
angličtina
Original language name
Impact of polymer-TLR-7/8 agonist (adjuvant) morphology on the potency and mechanism of CD8 T cell induction
Original language description
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.
Czech name
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Czech description
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Classification
Type
J<sub>imp</sub> - Article in a specialist periodical, which is included in the Web of Science database
CEP classification
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OECD FORD branch
10404 - Polymer science
Result continuities
Project
Result was created during the realization of more than one project. More information in the Projects tab.
Continuities
P - Projekt vyzkumu a vyvoje financovany z verejnych zdroju (s odkazem do CEP)
Others
Publication year
2019
Confidentiality
S - Úplné a pravdivé údaje o projektu nepodléhají ochraně podle zvláštních právních předpisů
Data specific for result type
Name of the periodical
Biomacromolecules
ISSN
1525-7797
e-ISSN
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Volume of the periodical
20
Issue of the periodical within the volume
2
Country of publishing house
US - UNITED STATES
Number of pages
17
Pages from-to
854-870
UT code for WoS article
000458937200029
EID of the result in the Scopus database
2-s2.0-85061283042