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

0464818 - ÚMCH 2017 RIV US eng J - Článek v odborném periodiku
Francica, J. R. - Lynn, G. M. - Laga, Richard - Joyce, M. G. - Ruckwardt, T. J. - Morabito, K. M. - Chen, M. - Chaudhuri, R. - Zhang, B. - Sastry, M. - Druz, A. - Ko, K. - Choe, M. - Pechar, Michal - Georgiev, I. S. - Kueltzo, L. A. - Seymour, L. W. - Mascola, J. R. - Kwong, P. D. - Graham, B. S. - Seder, R. A.
Thermoresponsive polymer nanoparticles co-deliver RSV F trimers with a TLR-7/8 adjuvant.
Bioconjugate Chemistry. Roč. 27, č. 10 (2016), s. 2372-2385. ISSN 1043-1802. E-ISSN 1520-4812
Grant CEP: GA ČR(CZ) GJ16-14957Y; GA MŠMT(CZ) LQ1604
Institucionální podpora: RVO:61389013
Klíčová slova: thermoresponsive polymers * polymer vaccines * toll-like receptor agonists
Kód oboru RIV: CD - Makromolekulární chemie
Impakt faktor: 4.818, rok: 2016

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(H)1 isotype anti-RSV F antibodies following vaccination. Moreover, coupling F trimers to TRP delivering TLR-7/8a resulted in similar to 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.
Trvalý link: http://hdl.handle.net/11104/0264112