title: Type B CpG oligodeoxynucleotides induce Th1 responses to peanut antigens: modulation of sensitization and utility in a truncated immunotherapy regimen in mice.
abstract: METHODS
  Peanut allergy stems from a Th2-biased immune response to peanut allergens leading to IgE production and allergic reactions upon ingestion.
  
  
  RESULTS
  A model of peanut allergy in C3H/HeJ mice was used to assess whether type A, B, or C CpG oligodeoxynucleotide (ODN) molecules would be effective in: (i) a prophylactic approach to prevent peanut allergy when administered simultaneously with a Th2-skewing adjuvant, and (ii) a therapeutic model to allow for shortened immunotherapy. Type B ODNs were extremely effective in inhibiting anaphylaxis in the sensitization protocol as evidenced by differences in symptom scores, body temperature, and mouse mast cell protease 1 release compared to sham treatment. In the therapeutic model, co-administration of type B ODN plus peanut proteins was highly effective in reducing anaphylactic reactions in mice with established peanut allergy. The therapeutic effect was accompanied by an increase in IFN-γ and peanut-IgG2a, without a significant decrease in peanut IgE or IL-4 responses.
  
  
  CONCLUSIONS
  CpG ODNs, especially type B, were highly effective in inducing Th1 responses in mice undergoing induction of peanut allergy, as well as in mice undergoing therapy for established peanut allergy. Interestingly, the IgE response was not significantly altered, suggesting that IgG antibodies may be enough to prevent peanut-induced anaphylaxis.
authors: Department of Pediatric Allergy and Immunology, Duke University Medical Center, Durham, NC 27599, USA. mike.kulis@unc.edu
authors: Mike
authors: M
authors: Kulis
authors: Balachandra
authors: B
authors: Gorentla
authors: A Wesley
authors: AW
authors: Burks
authors: Xiao-Ping
authors: XP
authors: Zhong
mesh_terms: D000276:Adjuvants, Immunologic / Q000494:pharmacology*; D000707:Anaphylaxis / Q000276:immunology / Q000517:prevention & control; D000818:Animals; D052179:Antigens, Plant / Q000276:immunology*; D010367:Arachis / Q000737:chemistry / Q000276:immunology*; D003713:Dendritic Cells / Q000276:immunology; D005260:Female; D007073:Immunoglobulin E / Q000276:immunology / Q000378:metabolism; D007074:Immunoglobulin G / Q000276:immunology; D007167:Immunotherapy; D007371:Interferon-gamma / Q000276:immunology; D018664:Interleukin-12 / Q000097:blood; D051379:Mice; D008809:Mice, Inbred C3H; D009838:Oligodeoxyribonucleotides / Q000494:pharmacology*; D021183:Peanut Hypersensitivity / Q000097:blood / Q000276:immunology / Q000517:prevention & control*; D018417:Th1 Cells / Q000276:immunology* / Q000378:metabolism; D014409:Tumor Necrosis Factor-alpha / Q000097:blood
chemical_list: D000276:Adjuvants, Immunologic; D052179:Antigens, Plant; C408982:CPG-oligonucleotide; D007074:Immunoglobulin G; D009838:Oligodeoxyribonucleotides; D014409:Tumor Necrosis Factor-alpha; D018664:Interleukin-12; D007073:Immunoglobulin E; D007371:Interferon-gamma
references: J Allergy Clin Immunol. 2010 Jul;126(1):31-2
references: 20620564
references: Clin Exp Allergy. 2010 Apr;40(4):598-606
references: 20184605
references: Biochemistry. 1989 Jan 10;28(1):391-5
references: 2706264
references: Ann Allergy Asthma Immunol. 2010 Dec;105(6):444-50
references: 21130382
references: J Allergy Clin Immunol. 2010 Jul;126(1):92-7.e5
references: 20538332
references: J Allergy Clin Immunol. 2009 Aug;124(2):292-300, 300.e1-97
references: 19577283
references: Int Arch Allergy Immunol. 2009;148(2):109-17
references: 18802355
references: J Allergy Clin Immunol. 2000 Jul;106(1 Pt 1):150-8
references: 10887318
references: J Allergy Clin Immunol. 2011 Mar;127(3):654-60
references: 21377034
references: J Allergy Clin Immunol. 2011 Jan;127(1):18-27; quiz 28-9
references: 21211639
references: J Allergy Clin Immunol. 2012 Feb;129(2):448-55, 455.e1-5
references: 22130425
references: Clin Exp Allergy. 2011 Sep;41(9):1226-34
references: 21729181
references: Nat Rev Drug Discov. 2006 Jun;5(6):471-84
references: 16763660
references: J Allergy Clin Immunol. 2011 Mar;127(3):640-6.e1
references: 21281959
references: J Allergy Clin Immunol. 2011 Jul;128(1):212-4
references: 21439625
references: Int Arch Allergy Immunol. 2007;143(1):10-20
references: 17191005
references: Immunology. 2004 Nov;113(3):293-303
references: 15500615
references: J Allergy Clin Immunol. 2007 Apr;119(4):1016-8
references: 17306354
references: N Engl J Med. 2006 Oct 5;355(14):1445-55
references: 17021320
references: Adv Drug Deliv Rev. 2009 Mar 28;61(3):195-204
references: 19211030
references: J Allergy Clin Immunol. 2008 Nov;122(5):984-91
references: 19000582
references: Int Immunopharmacol. 2008 Feb;8(2):351-61
references: 18182251
references: J Allergy Clin Immunol. 2011 Jan;127(1):81-8
references: 21093029
references: Clin Exp Allergy. 2005 Jun;35(6):757-66
references: 15969667
references: J Allergy Clin Immunol. 2007 Jan;119(1):199-205
references: 17208602
references: Eur J Immunol. 2004 Jan;34(1):251-62
references: 14971051
references: J Allergy Clin Immunol. 2010 Jul;126(1):83-91.e1
references: 20542324
references: Discov Med. 2011 Oct;12(65):319-28
references: 22031669
references: J Clin Invest. 2006 Mar;116(3):833-41
references: 16498503
references: Lancet. 2008 May 3;371(9623):1538-46
references: 18456104
references: Allergy. 2006 Jan;61(1):64-71
references: 16364158
references: J Immunol. 2006 Sep 15;177(6):3677-85
references: 16951327
references: J Immunol. 2004 Mar 1;172(5):3252-9
references: 14978133
references: J Immunol. 2006 Aug 15;177(4):2373-83
references: 16887999
references: J Allergy Clin Immunol. 2007 Sep;120(3):631-7
references: 17582479
references: J Immunol. 2006 Aug 1;177(3):1561-6
references: 16849463
references: Immunol Res. 2011 Apr;49(1-3):216-26
references: 21161431
references: J Exp Med. 2009 Aug 31;206(9):1941-55
references: 19667059
references: J Immunol Methods. 2006 Dec 20;317(1-2):71-9
references: 17070537
references: J Allergy Clin Immunol. 2004 Oct;114(4):915-21
references: 15480335
references: J Immunol. 2004 Jun 1;172(11):6978-87
references: 15153518