Thermoresponsive polymer nanoparticles co-deliver RSV F trimers with a TLR-7/8 adjuvant

Result code in IS VaVaI
<a href="https://www.isvavai.cz/riv?ss=detail&h=RIV%2F61389013%3A_____%2F16%3A00464818" target="_blank" >RIV/61389013:_____/16:00464818 - isvavai.cz</a>
Result on the web
<a href="http://dx.doi.org/10.1021/acs.bioconjchem.6b00370" target="_blank" >http://dx.doi.org/10.1021/acs.bioconjchem.6b00370</a>
DOI - Digital Object Identifier
<a href="http://dx.doi.org/10.1021/acs.bioconjchem.6b00370" target="_blank" >10.1021/acs.bioconjchem.6b00370</a>

Result language
angličtina
Original language name
Thermoresponsive polymer nanoparticles co-deliver RSV F trimers with a TLR-7/8 adjuvant
Original language description
Structure-based vaccine design has been used to develop immunogens that display conserved neutralization sites on pathogens such as HIV-1, respiratory syncytial virus (RSV), and influenza. Improving the immunogenicity of these designed immunogens with adjuvants will require formulations that do not alter protein antigenicity. Here, we show that nanoparticle-forming thermoresponsive polymers (TRP) allow for co-delivery of RSV fusion (F) protein trimers with Toll-like receptor 7 and 8 agonists (TLR-7/8a) to enhance protective immunity. Although primary amine conjugation of TLR-7/8a to F trimers severely disrupted the recognition of critical neutralizing epitopes, F trimers site-selectively coupled to TRP nanoparticles retained appropriate antigenicity and elicited high titers of prefusion-specific, TH1 isotype anti-RSV F antibodies following vaccination. Moreover, coupling F trimers to TRP delivering TLR-7/8a resulted in ∼3-fold higher binding and neutralizing antibody titers than soluble F trimers admixed with TLR-7/8a and conferred protection from intranasal RSV challenge. Overall, these data show that TRP nanoparticles may provide a broadly applicable platform for eliciting neutralizing antibodies to structure-dependent epitopes on RSV, influenza, HIV-1, or other pathogens.
Czech name
—
Czech description
—

Type
J<sub>x</sub> - Unclassified - Peer-reviewed scientific article (Jimp, Jsc and Jost)
CEP classification
CD - Macromolecular chemistry
OECD FORD branch
—

Project
Result was created during the realization of more than one project. More information in the Projects tab.
Continuities
I - Institucionalni podpora na dlouhodoby koncepcni rozvoj vyzkumne organizace

Publication year
2016
Confidentiality
S - Úplné a pravdivé údaje o projektu nepodléhají ochraně podle zvláštních právních předpisů

Similar results(10)