1 research outputs found
Thermoresponsive Polymer Nanoparticles Co-deliver RSV F Trimers with a TLR-7/8 Adjuvant
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,
T<sub>H</sub>1 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