3 years ago

Protein corona-mediated targeting of nano-carriers to B cells allows redirection of allergic immune responses

Nanoparticle (NP) based vaccines are attractive immunotherapy tools due to their capability to co-deliver antigen and adjuvant to antigen presenting cells. Their cellular distribution and serum protein interaction (“protein corona”) after systemic administration and its impact on functional properties of NP is poorly understood. Objectives We analyzed the relevance of the protein corona on cell type-selective uptake of dextran (DEX)-coated NP and determined the outcome of vaccination with NP that codeliver antigen and adjuvant in disease models of allergy. Methods The role of protein corona constituents for cellular binding/uptake of DEX-NP was analyzed in vitro and in vivo. DEX-NP conjugated with the model antigen ovalbumin (OVA), and immunostimulatory CpG-rich oligonucleotides (ODN) 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-NP triggered lectin-induced complement activation yielding deposition of activated complement C3 on the DEX-NP surface. In spleen, DEX-NP predominantly targeted B cells via their complement receptor CR1/2. The DEX-NP vaccine elicited much stronger OVA-specific IgG2a production than co-administered soluble OVA plus CpG ODN. B cell binding of the DEX-NP vaccine was critical for IgG2a production. Treatment of OVA-sensitized mice with the DEX-NP vaccine prevented the induction of anaphylactic shock and allergic asthma, accompanied by IgE inhibition. Conclusions Opsonization of lectin-coated NP by activated complement components results in selective B cell targeting. The intrinsic B cell targeting property of lectin-coated NP can be exploited for the treatment of allergic immune responses.

Publisher URL: www.sciencedirect.com/science

DOI: S0091674918301210

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