Thermoresponsive Polymer Nanoparticles Co-deliver RSV F Trimers with a TLR-7/8 Adjuvant
Language English Country United States Media print-electronic
Document type Journal Article, Research Support, Non-U.S. Gov't
Grant support
17720
Cancer Research UK - United Kingdom
- MeSH
- Adjuvants, Immunologic administration & dosage MeSH
- Mice, Inbred Strains MeSH
- Drug Delivery Systems methods MeSH
- Nanoparticles administration & dosage chemistry MeSH
- Antibodies, Neutralizing MeSH
- Polymers chemistry MeSH
- Viral Fusion Proteins administration & dosage chemistry MeSH
- Vaccines, Synthetic administration & dosage chemistry MeSH
- Chemistry Techniques, Synthetic MeSH
- Toll-Like Receptor 7 agonists MeSH
- Toll-Like Receptor 8 agonists MeSH
- Respiratory Syncytial Virus Vaccines administration & dosage immunology pharmacology MeSH
- Animals MeSH
- Check Tag
- Female MeSH
- Animals MeSH
- Publication type
- Journal Article MeSH
- Research Support, Non-U.S. Gov't MeSH
- Names of Substances
- Adjuvants, Immunologic MeSH
- F protein, human respiratory syncytial virus MeSH Browser
- Antibodies, Neutralizing MeSH
- Polymers MeSH
- Viral Fusion Proteins MeSH
- Vaccines, Synthetic MeSH
- TLR7 protein, human MeSH Browser
- TLR8 protein, human MeSH Browser
- Toll-Like Receptor 7 MeSH
- Toll-Like Receptor 8 MeSH
- Respiratory Syncytial Virus Vaccines MeSH
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.
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