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Title: Nanoparticle conjugation enhances the immunomodulatory effects of intranasally delivered CpG in house dust mite-allergic mice

Abstract

An emerging strategy in preventing and treating airway allergy consists of modulating the immune response induced against allergens in the lungs. CpG oligodeoxynucleotides have been investigated in airway allergy studies, but even if promising, efficacy requires further substantiation. We investigated the effect of pulmonary delivery of nanoparticle (NP)-conjugated CpG on lung immunity and found that NP-CpG led to enhanced recruitment of activated dendritic cells and to Th1 immunity compared to free CpG. We then evaluated if pulmonary delivery of NP-CpG could prevent and treat house dust mite-induced allergy by modulating immunity directly in lungs. When CpG was administered as immunomodulatory therapy prior to allergen sensitization, we found that NP-CpG significantly reduced eosinophilia, IgE levels, mucus production and Th2 cytokines, while free CpG had only a moderate effect on these parameters. In a therapeutic setting where CpG was administered after allergen sensitization, we found that although both free CpG and NP-CpG reduced eosinophilia and IgE levels to the same extent, NP conjugation of CpG significantly enhanced reduction of Th2 cytokines in lungs of allergic mice. Taken together, these data highlight benefits of NP conjugation and the relevance of NP-CpG as allergen-free therapy to modulate lung immunity and treat airway allergy.

Authors:
 [1];  [1];  [1];  [1];  [2];  [1];  [1]
  1. Ecole polytechnique fédérale de Lausanne (Switzerland). Institute of Bioengineering
  2. Univ. de Lausanne (UNIL) (Switzerland)
Publication Date:
Research Org.:
Argonne National Lab. (ANL), Argonne, IL (United States)
Sponsoring Org.:
USDOE; European Research Council (ERC); Swiss National Science Foundation (SNSF); USDOE Office of Science (SC), Basic Energy Sciences (BES) (SC-22). Materials Sciences and Engineering Division
OSTI Identifier:
1222943
Alternate Identifier(s):
OSTI ID: 1332964
Grant/Contract Number:  
AC02-06CH11357
Resource Type:
Accepted Manuscript
Journal Name:
Scientific Reports
Additional Journal Information:
Journal Volume: 5; Journal ID: ISSN 2045-2322
Publisher:
Nature Publishing Group
Country of Publication:
United States
Language:
English
Subject:
77 NANOSCIENCE AND NANOTECHNOLOGY; 59 BASIC BIOLOGICAL SCIENCES

Citation Formats

Ballester, Marie, Jeanbart, Laura, de Titta, Alexandre, Nembrini, Chiara, Marsland, Benjamin J., Hubbell, Jeffrey A., and Swartz, Melody A. Nanoparticle conjugation enhances the immunomodulatory effects of intranasally delivered CpG in house dust mite-allergic mice. United States: N. p., 2015. Web. doi:10.1038/srep14274.
Ballester, Marie, Jeanbart, Laura, de Titta, Alexandre, Nembrini, Chiara, Marsland, Benjamin J., Hubbell, Jeffrey A., & Swartz, Melody A. Nanoparticle conjugation enhances the immunomodulatory effects of intranasally delivered CpG in house dust mite-allergic mice. United States. doi:10.1038/srep14274.
Ballester, Marie, Jeanbart, Laura, de Titta, Alexandre, Nembrini, Chiara, Marsland, Benjamin J., Hubbell, Jeffrey A., and Swartz, Melody A. Mon . "Nanoparticle conjugation enhances the immunomodulatory effects of intranasally delivered CpG in house dust mite-allergic mice". United States. doi:10.1038/srep14274. https://www.osti.gov/servlets/purl/1222943.
@article{osti_1222943,
title = {Nanoparticle conjugation enhances the immunomodulatory effects of intranasally delivered CpG in house dust mite-allergic mice},
author = {Ballester, Marie and Jeanbart, Laura and de Titta, Alexandre and Nembrini, Chiara and Marsland, Benjamin J. and Hubbell, Jeffrey A. and Swartz, Melody A.},
abstractNote = {An emerging strategy in preventing and treating airway allergy consists of modulating the immune response induced against allergens in the lungs. CpG oligodeoxynucleotides have been investigated in airway allergy studies, but even if promising, efficacy requires further substantiation. We investigated the effect of pulmonary delivery of nanoparticle (NP)-conjugated CpG on lung immunity and found that NP-CpG led to enhanced recruitment of activated dendritic cells and to Th1 immunity compared to free CpG. We then evaluated if pulmonary delivery of NP-CpG could prevent and treat house dust mite-induced allergy by modulating immunity directly in lungs. When CpG was administered as immunomodulatory therapy prior to allergen sensitization, we found that NP-CpG significantly reduced eosinophilia, IgE levels, mucus production and Th2 cytokines, while free CpG had only a moderate effect on these parameters. In a therapeutic setting where CpG was administered after allergen sensitization, we found that although both free CpG and NP-CpG reduced eosinophilia and IgE levels to the same extent, NP conjugation of CpG significantly enhanced reduction of Th2 cytokines in lungs of allergic mice. Taken together, these data highlight benefits of NP conjugation and the relevance of NP-CpG as allergen-free therapy to modulate lung immunity and treat airway allergy.},
doi = {10.1038/srep14274},
journal = {Scientific Reports},
number = ,
volume = 5,
place = {United States},
year = {2015},
month = {9}
}

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Cited by: 15 works
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