Antigen delivery via hydrophilic PEG-b-PAGE-b-PLGA nanoparticles boosts vaccination induced T cell immunity

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• 作者：René ; Rietscher^a ; ¹ ; Matthias Schrö ; der^b ; ^c ; ¹ ; Julia Janke^d ; Justyna Czaplewska^e ; ^f ; Michael Gottschaldt^e ; ^f ; Regina Scherließ ; ^d ; Andrea Hanefeld^g ; Ulrich S. Schubert^e ; ^f ; Marc Schneider^h ; ; Percy A. Knolle^c ; ; Claus-Michael Lehr^a ; ^h ; ^{claus-michael.lehr@helmholtz-hzi.de" class="auth_mail" title="E-mail the corresponding author}
• 关键词：Poly(d ; l-lactide-co-glycolide) ; Polyethylene glycol ; Poly(allyl glycidyl ether) ; Vaccination ; Nanomedicines ; Cellular uptake
• 刊名：European Journal of Pharmaceutics and Biopharmaceutics
• 出版年：2016
• 出版时间：May 2016
• 年：2016
• 卷：102
• 期：Complete
• 页码：20-31
• 全文大小：983 K

文摘

Here, we evaluate the use of hydrophilic PEG-b-PAGE-b-PLGA (PPP) for the preparation of antigen loaded nanoparticles (NPs) as a platform for prophylactic vaccination. To investigate the suitability of PPP-NPs for antigen delivery, we used the double emulsion evaporation technique to prepare NPs of different sizes, antigen-loading efficiencies and -release kinetics for the model antigen Ovalbumin (OVA). Prior to applying the PPP-NPs in biological in vitro or in vivo models, all materials were tested for absence of cytotoxicity and endotoxins. While the uptake of NPs in antigen presenting cells was size but not polymer dependent, the efficiency of cross presentation of NP-associated antigen on MHC I molecules for CD8 T cell activation depended on the polymer type. T cell activation by antigen-presenting cells was significantly increased in vitro if antigen was delivered via PPP NPs compared to PLGA NPs or soluble OVA, although antigen content was the same in all tested formulations. Subcutaneous application of PPP-OVA-NPs even without adjuvants led to generation of potent CD8 T cell-mediated OVA-specific cytotoxicity in vivo that was more pronounced than after application of OVA alone or PLGA-OVA-NPs. Our data suggest that PPP-NPs can serve as platform for antigen-delivery in future vaccination formulations. Although PPP-NPs already bear intrinsic adjuvant-function, the complementation with TLR ligands loaded inside NPs may further strengthen the immune response to a point, where it might be possible to use it as a therapeutic vaccine to break immune tolerance in chronic disease states.