title: Mechanisms underlying allergy vaccination with recombinant hypoallergenic allergen derivatives.
abstract: Hundred years ago therapeutic vaccination with allergen-containing extracts has been introduced as a clinically effective, disease-modifying, allergen-specific and long-lasting form of therapy for allergy, a hypersensitivity disease affecting more than 25% of the population. Today, the structures of most of the disease-causing allergens have been elucidated and recombinant hypoallergenic allergen derivatives with reduced allergenic activity have been engineered to reduce side effects during allergen-specific immunotherapy (SIT). These recombinant hypoallergens have been characterized in vitro, in experimental animal models and in clinical trials in allergic patients. This review provides a summary of the molecular, immunological and preclinical evaluation criteria applied for this new generation of allergy vaccines. Furthermore, we summarize the mechanisms underlying SIT with recombinant hypoallergens which are thought to be responsible for their therapeutic effect.
authors.affiliation: Division of Immunopathology, Department of Pathophysiology and Allergy Research, Center of Pathophysiology, Infectiology and Immunology, Medical University of Vienna, Waehringer Guertel 18-20, A-1090 Vienna, Austria. birgit.linhart@meduniwien.ac.at
authors.forename: Birgit
authors.initials: B
authors.lastname: Linhart
authors.forename: Rudolf
authors.initials: R
authors.lastname: Valenta
mesh_terms: D000485:Allergens / Q000276:immunology / Q000627:therapeutic use*; D000818:Animals; D002986:Clinical Trials as Topic; D003888:Desensitization, Immunologic / Q000009:adverse effects / Q000379:methods*; D006801:Humans; D006967:Hypersensitivity / Q000628:therapy*; D007073:Immunoglobulin E / Q000276:immunology; D014611:Vaccination / Q000009:adverse effects / Q000379:methods*; D014612:Vaccines / Q000276:immunology / Q000627:therapeutic use*
chemical_list: D000485:Allergens; D014612:Vaccines; D007073:Immunoglobulin E
references.citation: Int Arch Allergy Immunol. 2011;154(3):258-63
references.pmid: 20861648
references.citation: Clin Exp Allergy. 2007 Feb;37(2):251-60
references.pmid: 17250698
references.citation: Clin Exp Allergy. 2003 Sep;33(9):1198-208
references.pmid: 12956739
references.citation: J Immunol. 2002 Nov 15;169(10):6005-11
references.pmid: 12421987
references.citation: Nat Rev Immunol. 2006 Oct;6(10):761-71
references.pmid: 16998509
references.citation: J Immunol. 2004 May 1;172(9):5684-92
references.pmid: 15100313
references.citation: Immunology. 1970 May;18(5):705-22
references.pmid: 4192674
references.citation: Allergy. 2011 Jun;66(6):775-83
references.pmid: 21352238
references.citation: J Immunol. 2004 Oct 15;173(8):5258-67
references.pmid: 15470071
references.citation: Clin Exp Allergy. 2000 Aug;30(8):1076-84
references.pmid: 10931114
references.citation: Proc Natl Acad Sci U S A. 2004 Oct 5;101 Suppl 2:14677-82
references.pmid: 15310844
references.citation: Int Arch Allergy Immunol. 2001 Jan-Mar;124(1-3):70-2
references.pmid: 11306930
references.citation: Nat Rev Immunol. 2002 Jun;2(6):446-53
references.pmid: 12093011
references.citation: J Immunol. 2007 Oct 15;179(8):5309-16
references.pmid: 17911617
references.citation: J Biol Chem. 1994 Nov 11;269(45):28323-8
references.pmid: 7525573
references.citation: J Immunol. 2004 Nov 1;173(9):5872-9
references.pmid: 15494541
references.citation: J Immunol. 2011 May 1;186(9):5333-44
references.pmid: 21451110
references.citation: J Allergy Clin Immunol. 1991 Jun;87(6):1120-7
references.pmid: 2045616
references.citation: FEBS Lett. 1998 Sep 4;434(3):255-60
references.pmid: 9742934
references.citation: J Allergy Clin Immunol. 2010 Nov;126(5):1024-31, 1031.e1-8
references.pmid: 20638112
references.citation: J Immunol. 2007 Dec 1;179(11):7624-34
references.pmid: 18025208
references.citation: J Clin Invest. 1997 Apr 1;99(7):1673-81
references.pmid: 9120011
references.citation: J Allergy Clin Immunol. 1998 Feb;101(2 Pt 1):258-64
references.pmid: 9500760
references.citation: J Invest Dermatol. 2001 Oct;117(4):848-51
references.pmid: 11676821
references.citation: Int Arch Allergy Immunol. 2002 May;128(1):15-23
references.pmid: 12037397
references.citation: J Allergy Clin Immunol. 2003 Apr;111(4):777-83
references.pmid: 12704357
references.citation: Curr Opin Immunol. 2005 Dec;17(6):646-55
references.pmid: 16229996
references.citation: J Immunol. 2002 Nov 1;169(9):5137-44
references.pmid: 12391230
references.citation: J Allergy Clin Immunol. 2008 Feb;121(2):528-530.e1
references.pmid: 18269928
references.citation: N Engl J Med. 1999 Aug 12;341(7):468-75
references.pmid: 10441602
references.citation: Clin Exp Allergy. 2009 Jul;39(7):1088-98
references.pmid: 19400901
references.citation: J Immunol. 1993 Apr 15;150(8 Pt 1):3643-50
references.pmid: 8468493
references.citation: J Exp Med. 1999 Jun 21;189(12):1885-94
references.pmid: 10377184
references.citation: J Immunol. 2007 May 15;178(10):6290-6
references.pmid: 17475857
references.citation: Clin Exp Allergy. 2008 Aug;38(8):1400-8
references.pmid: 18564332
references.citation: Eur J Immunol. 2005 Nov;35(11):3268-76
references.pmid: 16206231
references.citation: J Allergy Clin Immunol. 1993 Jul;92(1 Pt 1):105-13
references.pmid: 8335846
references.citation: J Allergy Clin Immunol. 2008 Nov;122(5):951-60
references.pmid: 19000581
references.citation: N Engl J Med. 2006 Oct 5;355(14):1445-55
references.pmid: 17021320
references.citation: Int Arch Allergy Immunol. 1998 Nov;117(3):160-6
references.pmid: 9935306
references.citation: J Immunol. 1993 Feb 1;150(3):1047-54
references.pmid: 7678615
references.citation: J Allergy Clin Immunol. 1998 Oct;102(4 Pt 1):558-62
references.pmid: 9802362
references.citation: J Allergy Clin Immunol. 2005 Sep;116(3):608-13
references.pmid: 16159631
references.citation: J Allergy Clin Immunol. 1995 Jan;95(1 Pt 1):77-87
references.pmid: 7822667
references.citation: J Allergy Clin Immunol. 2007 Sep;120(3):602-9
references.pmid: 17561242
references.citation: Clin Exp Allergy. 2008 Aug;38(8):1290-301
references.pmid: 18510696
references.citation: J Immunol. 1999 Sep 1;163(5):2944-52
references.pmid: 10453043
references.citation: J Allergy Clin Immunol. 1997 Oct;100(4):505-10
references.pmid: 9338545
references.citation: J Allergy Clin Immunol. 1997 Dec;100(6 Pt 1):721-7
references.pmid: 9438477
references.citation: J Allergy Clin Immunol. 1999 Nov;104(5):969-77
references.pmid: 10550741
references.citation: Methods. 2004 Mar;32(3):241-8
references.pmid: 14962758
references.citation: J Immunol. 2009 Feb 15;182(4):2141-51
references.pmid: 19201867
references.citation: FASEB J. 1998 Feb;12(2):231-42
references.pmid: 9472988
references.citation: Clin Exp Allergy. 2004 Oct;34(10):1525-33
references.pmid: 15479266
references.citation: Am J Respir Crit Care Med. 1996 Dec;154(6 Pt 1):1623-8
references.pmid: 8970345
references.citation: J Immunol. 2009 May 15;182(10):6298-306
references.pmid: 19414783
references.citation: J Allergy Clin Immunol. 2001 Jun;107(6):1069-76
references.pmid: 11398087
references.citation: Eur J Immunol. 2002 Jan;32(1):270-80
references.pmid: 11782018
references.citation: FASEB J. 2001 Sep;15(11):2042-4
references.pmid: 11511525
references.citation: J Allergy Clin Immunol. 2011 Jun;127(6):1562-70.e6
references.pmid: 21411130
references.citation: Clin Exp Allergy. 2000 Oct;30(10):1423-9
references.pmid: 10998019
references.citation: J Immunol. 2000 Dec 1;165(11):6653-9
references.pmid: 11086111
references.citation: Eur J Clin Invest. 2008 Apr;38(4):260-7
references.pmid: 18339006
references.citation: J Allergy Clin Immunol. 2008 Mar;121(3):603-6
references.pmid: 18328889
references.citation: J Immunol. 2001 May 15;166(10):6057-65
references.pmid: 11342623
references.citation: Curr Opin Investig Drugs. 2010 May;11(5):586-96
references.pmid: 20419605
references.citation: Clin Exp Allergy. 2004 Jan;34(1):115-22
references.pmid: 14720271
references.citation: Int Arch Allergy Immunol. 2008;145(3):193-206
references.pmid: 17912007
references.citation: Clin Exp Allergy. 2002 Oct;32(10):1448-53
references.pmid: 12372124
references.citation: Eur J Clin Invest. 2009 May;39(5):429-36
references.pmid: 19302561
references.citation: Clin Exp Allergy. 2007 Mar;37(3):441-50
references.pmid: 17359394
references.citation: J Exp Med. 1935 Nov 30;62(6):733-50
references.pmid: 19870445
references.citation: Mol Immunol. 2011 Jan;48(4):431-41
references.pmid: 21093057
references.citation: J Allergy Clin Immunol. 2011 Jul;128(1):178-184.e7
references.pmid: 21513971
references.citation: J Allergy Clin Immunol. 2007 Apr;119(4):1013-6
references.pmid: 17292956
references.citation: Protein Sci. 2004 Nov;13(11):2970-8
references.pmid: 15459335
references.citation: J Allergy Clin Immunol. 2011 Apr;127(4):860-4
references.pmid: 21458656
references.citation: Int Arch Allergy Immunol. 2001 Sep;126(1):32-40
references.pmid: 11641604
references.citation: J Allergy Clin Immunol. 2002 Jul;110(1):102-9
references.pmid: 12110828
references.citation: Int Arch Allergy Immunol. 2004 Aug;134(4):324-31
references.pmid: 15240999
references.citation: J Allergy Clin Immunol. 1996 Dec;98(6 Pt 1):1028-34
references.pmid: 8977501
references.citation: J Exp Med. 1964 Oct 1;120:507-30
references.pmid: 14212116
references.citation: Mol Immunol. 1998 Nov;35(16):1017-23
references.pmid: 10068036
references.citation: Int Arch Allergy Immunol. 2007;142(2):133-44
references.pmid: 17057411
references.citation: J Allergy Clin Immunol. 2011 Nov;128(5):1022-30.e1-7
references.pmid: 21571358
references.citation: Int Arch Allergy Immunol. 2005 Sep;138(1):59-66
references.pmid: 16103688
references.citation: J Allergy Clin Immunol. 2002 Feb;109(2):251-6
references.pmid: 11842293
references.citation: FASEB J. 2001 Sep;15(11):2045-7
references.pmid: 11511511
references.citation: J Allergy Clin Immunol. 1998 Oct;102(4 Pt 1):579-91
references.pmid: 9802365
references.citation: Clin Exp Allergy. 2008 Sep;38(9):1514-25
references.pmid: 18564326
references.citation: J Immunol. 2007 Aug 1;179(3):1730-9
references.pmid: 17641039
references.citation: Mol Immunol. 2008 May;45(9):2486-98
references.pmid: 18295887
references.citation: J Immunol. 2008 Oct 1;181(7):4864-73
references.pmid: 18802090
references.citation: Int Arch Allergy Immunol. 1998 Nov;117(3):167-73
references.pmid: 9831803
references.citation: Clin Exp Allergy. 2004 Mar;34(3):420-8
references.pmid: 15005736
references.citation: Int Arch Allergy Immunol. 2006;141(2):119-29
references.pmid: 16864979
references.citation: Allergy. 2009 Apr;64(4):569-80
references.pmid: 19243361
references.citation: J Allergy Clin Immunol. 2005 Aug;116(2):347-54
references.pmid: 16083789
references.citation: J Immunol Methods. 2006 Dec 20;317(1-2):71-9
references.pmid: 17070537
references.citation: Biol Chem. 2008 Jul;389(7):925-33
references.pmid: 18627317
references.citation: Clin Exp Allergy. 2003 May;33(5):669-75
references.pmid: 12752597
references.citation: Int Arch Allergy Immunol. 2004 Jan;133(1):84-100
references.pmid: 14726635
references.citation: Clin Exp Allergy. 2010 Mar;40(3):385-97
references.pmid: 20210812
references.citation: Annu Rev Immunol. 2010;28:211-41
references.pmid: 20192803
references.citation: Clin Exp Allergy. 2010 Sep;40(9):1346-52
references.pmid: 20604801
references.citation: J Immunol. 1998 Jun 15;160(12):6137-44
references.pmid: 9637531
references.citation: Immunol Rev. 2001 Feb;179:119-27
references.pmid: 11292015
references.citation: J Immunol. 1991 Dec 1;147(11):3768-73
references.pmid: 1940366
references.citation: J Allergy Clin Immunol. 2006 Jan;117(1):59-66
references.pmid: 16387585