TY - JOUR
T1 - Protein corona–mediated targeting of nanocarriers to B cells allows redirection of allergic immune responses
AU - Shen, Limei
AU - Tenzer, Stefan
AU - Storck, Wiebke
AU - Hobernik, Dominika
AU - Raker, Verena Katherina
AU - Fischer, Karl
AU - Decker, Sandra
AU - Dzionek, Andrzej
AU - Krauthäuser, Susanne
AU - Diken, Mustafa
AU - Nikolaev, Alexej
AU - Maxeiner, Joachim
AU - Schuster, Petra
AU - Kappel, Cinja
AU - Verschoor, Admar
AU - Schild, Hansjörg
AU - Grabbe, Stephan
AU - Bros, Matthias
N1 - Publisher Copyright:
© 2018 The Authors
Copyright:
Copyright 2018 Elsevier B.V., All rights reserved.
PY - 2018/11
Y1 - 2018/11
N2 - Background: Nanoparticle (NP)–based vaccines are attractive immunotherapy tools because of their capability to codeliver antigen and adjuvant to antigen-presenting cells. Their cellular distribution and serum protein interaction (“protein corona”) after systemic administration and their effect on the functional properties of NPs is poorly understood. Objectives: We analyzed the relevance of the protein corona on cell type–selective uptake of dextran-coated NPs and determined the outcome of vaccination with NPs that codeliver antigen and adjuvant in disease models of allergy. Methods: The role of protein corona constituents for cellular binding/uptake of dextran-coated ferrous nanoparticles (DEX-NPs) was analyzed both in vitro and in vivo. DEX-NPs conjugated with the model antigen ovalbumin (OVA) and immunostimulatory CpG-rich oligodeoxynucleotides were administered to monitor the induction of cellular and humoral immune responses. Therapeutic effects of this DEX-NP vaccine in mouse models of OVA-induced anaphylaxis and allergic asthma were assessed. Results: DEX-NPs triggered lectin-induced complement activation, yielding deposition of activated complement factor 3 on the DEX-NP surface. In the spleen DEX-NPs targeted predominantly B cells through complement receptors 1 and 2. The DEX-NP vaccine elicited much stronger OVA-specific IgG2a production than coadministered soluble OVA plus CpG oligodeoxynucleotides. B-cell binding of the DEX-NP vaccine was critical for IgG2a production. Treatment of OVA-sensitized mice with the DEX-NP vaccine prevented induction of anaphylactic shock and allergic asthma accompanied by IgE inhibition. Conclusions: Opsonization of lectin-coated NPs by activated complement components results in selective B-cell targeting. The intrinsic B-cell targeting property of lectin-coated NPs can be exploited for treatment of allergic immune responses.
AB - Background: Nanoparticle (NP)–based vaccines are attractive immunotherapy tools because of their capability to codeliver antigen and adjuvant to antigen-presenting cells. Their cellular distribution and serum protein interaction (“protein corona”) after systemic administration and their effect on the functional properties of NPs is poorly understood. Objectives: We analyzed the relevance of the protein corona on cell type–selective uptake of dextran-coated NPs and determined the outcome of vaccination with NPs that codeliver antigen and adjuvant in disease models of allergy. Methods: The role of protein corona constituents for cellular binding/uptake of dextran-coated ferrous nanoparticles (DEX-NPs) was analyzed both in vitro and in vivo. DEX-NPs conjugated with the model antigen ovalbumin (OVA) and immunostimulatory CpG-rich oligodeoxynucleotides were administered to monitor the induction of cellular and humoral immune responses. Therapeutic effects of this DEX-NP vaccine in mouse models of OVA-induced anaphylaxis and allergic asthma were assessed. Results: DEX-NPs triggered lectin-induced complement activation, yielding deposition of activated complement factor 3 on the DEX-NP surface. In the spleen DEX-NPs targeted predominantly B cells through complement receptors 1 and 2. The DEX-NP vaccine elicited much stronger OVA-specific IgG2a production than coadministered soluble OVA plus CpG oligodeoxynucleotides. B-cell binding of the DEX-NP vaccine was critical for IgG2a production. Treatment of OVA-sensitized mice with the DEX-NP vaccine prevented induction of anaphylactic shock and allergic asthma accompanied by IgE inhibition. Conclusions: Opsonization of lectin-coated NPs by activated complement components results in selective B-cell targeting. The intrinsic B-cell targeting property of lectin-coated NPs can be exploited for treatment of allergic immune responses.
UR - http://www.scopus.com/inward/record.url?scp=85042623973&partnerID=8YFLogxK
U2 - 10.1016/j.jaci.2017.08.049
DO - 10.1016/j.jaci.2017.08.049
M3 - Journal articles
C2 - 29382591
AN - SCOPUS:85042623973
SN - 0091-6749
VL - 142
SP - 1558
EP - 1570
JO - Journal of Allergy and Clinical Immunology
JF - Journal of Allergy and Clinical Immunology
IS - 5
ER -