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.
- MeSH
- adjuvancia imunologická aplikace a dávkování MeSH
- inbrední kmeny myší MeSH
- lékové transportní systémy metody MeSH
- nanočástice aplikace a dávkování chemie MeSH
- neutralizující protilátky MeSH
- polymery chemie MeSH
- proteiny virové fúze aplikace a dávkování chemie MeSH
- syntetické vakcíny aplikace a dávkování chemie MeSH
- techniky syntetické chemie MeSH
- toll-like receptor 7 agonisté MeSH
- toll-like receptor 8 agonisté MeSH
- vakcíny proti respiračnímu syncyciálnímu viru aplikace a dávkování imunologie farmakologie MeSH
- zvířata MeSH
- Check Tag
- ženské pohlaví MeSH
- zvířata MeSH
- Publikační typ
- časopisecké články MeSH
