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...
| Glavni autori: | , , , , , , , , , , , , , , , , , , , , |
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| Format: | Journal article |
| Jezik: | English |
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American Chemical Society
2016
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| _version_ | 1826280726179348480 |
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| author | Francica, JR Lynn, GM Laga, R Joyce, MG Ruckwardt, TJ Morabito, KM Chen, M Chaudhuri, R Zhang, B Sastry, M Druz, A Ko, K Choe, M Pechar, M Georgiev, IS Kueltzo, LA Seymour, LW Mascola, JR Kwong, PD Graham, BS Seder, RA |
| author_facet | Francica, JR Lynn, GM Laga, R Joyce, MG Ruckwardt, TJ Morabito, KM Chen, M Chaudhuri, R Zhang, B Sastry, M Druz, A Ko, K Choe, M Pechar, M Georgiev, IS Kueltzo, LA Seymour, LW Mascola, JR Kwong, PD Graham, BS Seder, RA |
| author_sort | Francica, JR |
| collection | OXFORD |
| 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. |
| first_indexed | 2024-03-07T00:18:02Z |
| format | Journal article |
| id | oxford-uuid:7b8766f2-4859-43a8-8d13-a09da4d9dac7 |
| institution | University of Oxford |
| language | English |
| last_indexed | 2024-03-07T00:18:02Z |
| publishDate | 2016 |
| publisher | American Chemical Society |
| record_format | dspace |
| spelling | oxford-uuid:7b8766f2-4859-43a8-8d13-a09da4d9dac72022-03-26T20:51:17ZThermoresponsive polymer nanoparticles co-deliver RSV F trimers with a TLR-7/8 adjuvantJournal articlehttp://purl.org/coar/resource_type/c_dcae04bcuuid:7b8766f2-4859-43a8-8d13-a09da4d9dac7EnglishSymplectic Elements at OxfordAmerican Chemical Society2016Francica, JRLynn, GMLaga, RJoyce, MGRuckwardt, TJMorabito, KMChen, MChaudhuri, RZhang, BSastry, MDruz, AKo, KChoe, MPechar, MGeorgiev, ISKueltzo, LASeymour, LWMascola, JRKwong, PDGraham, BSSeder, RAStructure-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. |
| spellingShingle | Francica, JR Lynn, GM Laga, R Joyce, MG Ruckwardt, TJ Morabito, KM Chen, M Chaudhuri, R Zhang, B Sastry, M Druz, A Ko, K Choe, M Pechar, M Georgiev, IS Kueltzo, LA Seymour, LW Mascola, JR Kwong, PD Graham, BS Seder, RA Thermoresponsive polymer nanoparticles co-deliver RSV F trimers with a TLR-7/8 adjuvant |
| title | Thermoresponsive polymer nanoparticles co-deliver RSV F trimers with a TLR-7/8 adjuvant |
| title_full | Thermoresponsive polymer nanoparticles co-deliver RSV F trimers with a TLR-7/8 adjuvant |
| title_fullStr | Thermoresponsive polymer nanoparticles co-deliver RSV F trimers with a TLR-7/8 adjuvant |
| title_full_unstemmed | Thermoresponsive polymer nanoparticles co-deliver RSV F trimers with a TLR-7/8 adjuvant |
| title_short | Thermoresponsive polymer nanoparticles co-deliver RSV F trimers with a TLR-7/8 adjuvant |
| title_sort | thermoresponsive polymer nanoparticles co deliver rsv f trimers with a tlr 7 8 adjuvant |
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