PMID- 19243361
OWN - NLM
STAT- MEDLINE
DCOM- 20090526
LR  - 20181201
IS  - 1398-9995 (Electronic)
IS  - 0105-4538 (Linking)
VI  - 64
IP  - 4
DP  - 2009 Apr
TI  - Reducing allergenicity by altering allergen fold: a mosaic protein of Phl p 1 for 
      allergy vaccination.
PG  - 569-80
LID - 10.1111/j.1398-9995.2008.01910.x [doi]
AB  - BACKGROUND: The major timothy grass pollen allergen, Phl p 1, resembles the 
      allergenic epitopes of natural group I grass pollen allergens and is recognized 
      by more than 95% of grass-pollen-allergic patients. Our objective was the 
      construction, purification and immunologic characterization of a genetically 
      modified derivative of the major timothy grass pollen allergen, Phl p 1 for 
      immunotherapy of grass pollen allergy. METHODS: A mosaic protein was generated by 
      PCR-based re-assembly and expression of four cDNAs coding for Phl p 1 fragments 
      and compared to the Phl p 1 wild-type by circular dichroism analysis, 
      immunoglobulin E (IgE)-binding capacity, basophil activation assays and 
      enzyme-linked immunosorbent assay competition assays. Immune responses to the 
      derivative were studied in BALB/c mice. RESULTS: Grass-pollen-allergic patients 
      exhibited greater than an 85% reduction in IgE reactivity to the mosaic as 
      compared with the Phl p 1 allergen and basophil activation experiments confirmed 
      the reduced allergenic activity of the mosaic. It also induced less Phl p 
      1-specific IgE antibodies than Phl p 1 upon immunization of mice. However, 
      immunization of mice and rabbits with the mosaic induced IgG antibodies that 
      inhibited patients' IgE-binding to the wild-type allergen and Phl p 1-induced 
      degranulation of basophils. CONCLUSION: We have developed a strategy based on 
      rational molecular reassembly to convert one of the clinically most relevant 
      allergens into a hypoallergenic derivative for allergy vaccination.
FAU - Ball, T
AU  - Ball T
AD  - Department of Pathophysiology, Center for Physiology, Pathophysiology and 
      Immunology, Medical University of Vienna, Austria.
FAU - Linhart, B
AU  - Linhart B
FAU - Sonneck, K
AU  - Sonneck K
FAU - Blatt, K
AU  - Blatt K
FAU - Herrmann, H
AU  - Herrmann H
FAU - Valent, P
AU  - Valent P
FAU - Stoecklinger, A
AU  - Stoecklinger A
FAU - Lupinek, C
AU  - Lupinek C
FAU - Thalhamer, J
AU  - Thalhamer J
FAU - Fedorov, A A
AU  - Fedorov AA
FAU - Almo, S C
AU  - Almo SC
FAU - Valenta, R
AU  - Valenta R
LA  - eng
PT  - Journal Article
PT  - Research Support, Non-U.S. Gov't
DEP - 20090219
PL  - Denmark
TA  - Allergy
JT  - Allergy
JID - 7804028
RN  - 0 (Allergens)
RN  - 0 (Epitopes, T-Lymphocyte)
RN  - 0 (Immunoglobulin G)
RN  - 0 (Plant Proteins)
RN  - 0 (Recombinant Proteins)
RN  - 160227-82-7 (PHLPI protein, Phleum pratense)
RN  - 37341-29-0 (Immunoglobulin E)
RN  - 820484N8I3 (Histamine)
SB  - IM
MH  - Adult
MH  - Aged
MH  - Allergens/*biosynthesis/chemistry/*immunology
MH  - Amino Acid Sequence
MH  - Animals
MH  - Basophils/immunology/metabolism
MH  - Desensitization, Immunologic/*methods
MH  - Epitopes, T-Lymphocyte/chemistry/immunology
MH  - Female
MH  - Histamine/biosynthesis/immunology
MH  - Humans
MH  - Immunoglobulin E/blood/immunology
MH  - Immunoglobulin G/blood/immunology
MH  - Lymphocyte Activation/immunology
MH  - Male
MH  - Mice
MH  - Mice, Inbred BALB C
MH  - Middle Aged
MH  - Molecular Sequence Data
MH  - Plant Proteins/*biosynthesis/chemistry/*immunology
MH  - Polymerase Chain Reaction
MH  - Protein Structure, Quaternary
MH  - Rabbits
MH  - Rats
MH  - Recombinant Proteins/*biosynthesis/chemical synthesis/*immunology
MH  - Rhinitis, Allergic, Seasonal/immunology/prevention & control
MH  - Spectrometry, Mass, Matrix-Assisted Laser Desorption-Ionization
MH  - T-Lymphocytes/immunology
EDAT- 2009/02/27 09:00
MHDA- 2009/05/27 09:00
CRDT- 2009/02/27 09:00
PHST- 2009/02/27 09:00 [entrez]
PHST- 2009/02/27 09:00 [pubmed]
PHST- 2009/05/27 09:00 [medline]
AID - ALL1910 [pii]
AID - 10.1111/j.1398-9995.2008.01910.x [doi]
PST - ppublish
SO  - Allergy. 2009 Apr;64(4):569-80. doi: 10.1111/j.1398-9995.2008.01910.x. Epub 2009 
      Feb 19.