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J Allergy Clin Immunol. 2018 Nov;142(5):1558-1570. doi: 10.1016/j.jaci.2017.08.049. Epub 2018 Jan 31.

Protein corona-mediated targeting of nanocarriers to B cells allows redirection of allergic immune responses.

Author information

1
Department of Dermatology, University of Mainz Medical Center, Mainz, Germany.
2
Institute for Immunology, University of Mainz Medical Center, Mainz, Germany.
3
Department of Physical Chemistry, University of Mainz, Mainz, Germany.
4
Miltenyi Biotec GmbH, Bergisch Gladbach, Germany.
5
TRON-Translational Oncology at the University Medical Center of the Johannes Gutenberg University gGmbH, Mainz, Germany.
6
Institute for Molecular Medicine, University of Mainz Medical Center, Mainz, Germany.
7
Asthma Core Facility, Research Center for Immunotherapy, University of Mainz Medical Center, Mainz, Germany.
8
Institute for Systemic Inflammation Research, Universität zu Lübeck, Lübeck, Germany.
9
Department of Dermatology, University of Mainz Medical Center, Mainz, Germany. Electronic address: stephan.grabbe@unimedizin-mainz.de.

Abstract

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.

KEYWORDS:

B cells; Dendritic cells; IgG(2a); antibody; complement; complement factor 3; lectin pathway

PMID:
29382591
DOI:
10.1016/j.jaci.2017.08.049
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