Allergy is a disorder of the immune system which is a form of hypersensitivity. Allergic reactions occur to normally harmless environmental substances known as allergens; these reactions are acquired, predictable, and rapid. Strictly, allergy is one of four forms of hypersensitivity and is called type I (or immediate) hypersensitivity. It is characterized by excessive activation of certain white blood cells called mast cells and basophils by a type of antibody known as IgE, resulting in an extreme inflammatory response. Common allergic reactions include eczema, hives, hay fever, asthma attacks, food allergies, and reactions to the venom of stinging insects such as wasps and bees.
Mild allergies like hay fever are highly prevalent in the human population and cause symptoms such as allergic conjunctivitis, itchiness, and runny nose. Allergies can play a major role in conditions such as asthma. In some people, severe allergies to environmental or dietary allergens or to medication may result in life-threatening anaphylactic reactions.
A variety of tests now exist to diagnose allergic conditions; these include testing the skin for responses to known allergens or analyzing the blood for the presence and levels of allergen-specific IgE. Treatments for allergies include allergen avoidance, use of anti-histamines, steroids or other oral medications, immunotherapy to desensitize the response to allergen, and targeted therapy (Wiki: Allergy).
Molecule Role Annotation :
A model of allergic airway disease that develops after ovalbumin (OVA) sensitization and challenge was used. Intranasal Ang-1 treatment prevented the OVA-induced eosinophilic lung infiltration, attenuated the increase in IL-5 and IL-13, and reduced eotaxin and vascular cell adhesion molecule 1 expression. These antiinflammatory actions of Ang-1 coincided with higher levels of IkappaB and decreased nuclear factor-kappaB binding activity. More importantly, Ang-1 reversed the OVA-induced increase in tissue resistance and elastance, improving lung function. We conclude that Ang-1 levels are decreased in asthma and that administration of Ang-1 might be of therapeutic value because it prevents the increased responsiveness of the airways to constrictors and ameliorates inflammation (Simoes et al., 2008).
Molecule Role Annotation :
Study investigated the effects of neutralizing anti-B7-H3 mAb in a mouse model of allergic asthma. Administration of anti-B7-H3 mAb significantly reduced airway hyperreactivity with a concomitant decrease in eosinophils in the lung as compared with control IgG-treated mice. Treatment with anti-B7-H3 mAb also resulted in decreased production of Th2 cytokines (IL-4, IL-5, and IL-13) in the draining lymph node cells (Nagashima et al., 2008).
Molecule Role Annotation :
Study examined the in vivo role of these costimulatory molecules in the pathogenesis of Th2-mediated allergen-induced airway hyperresponsiveness in a murine model of asthma. Administration of rat anti-mouse B7-2 (Cd86) mAb to OVA-treated mice abolished allergen-induced airway hyperresponsiveness, pulmonary eosinophilia, and elevations in serum IgG1 and IgE levels. Anti-B7-2 treatment of OVA-treated mice reduced both total lung IL-4 and IL-5 mRNA and bronchoalveolar lavage fluid IL-4 and IL-5 protein levels (Keane-Myers et al., 1998).
Molecule Role Annotation :
The delivery of DC-FasL into ovalbumin (OVA)-immunized allergic mice decreased the airway hyper-responsiveness (AHR). The administration of DC-FasL in Th2-cell-induced allergic mice caused significantly decreased AHR, airway inflammation, and IL-4, IL-5 and IL-13 production. Furthermore, the numbers of OVA-specific T cells were decreased in the lung of mice receiving DC-FasL. These results demonstrate that FasL-expressing dendritic cells might be applied for the modulation of allergic responses (Chuang et al., 2006).
Molecule Role Annotation :
The present experiments were undertaken to examine the effect of pUMVC3-hFLex, an active plasmid, mammalian expression vector for the secretion of Flt3-L, in a chronic model of allergic airway inflammation that was established in Balb/c mice by sensitization and challenge with ovalbumin (OVA). Treatment with pUMVC3-hFLex completely reversed established airway hyperresponsiveness (AHR) (p < 0.05), and this effect continued even after several exposures to the allergen (p < 0.05). pUMVC3-hFLex treatment prevented the development of goblet cell hyperplasia and subepithelial fibrosis, and significantly reduced serum levels of IL-4 and IL-5, and increased serum IL-10 levels (p < 0.05) with no effect on serum IL-13 (Edwan and Agrawal, 2007).
>NP_001344150.1 interleukin-18 isoform a precursor [Mus musculus]
MAAMSEDSCVNFKEMMFIDNTLYFIPEENGDLESDNFGRLHCTTAVIRNINDQVLFVDKRQPVFEDMTDI
DQSASEPQTRLIIYMYKDSEVRGLAVTLSVKDSKMSTLSCKNKIISFEEMDPPENIDDIQSDLIFFQKRV
PGHNKMEFESSLYEGHFLACQKEDDAFKLILKKKDENGDKSVMFTLTNLHQS
Molecule Role :
Protective antigen
Molecule Role Annotation :
Researchers developed a DNA vaccination plasmid containing OVA cDNA fused to IL-18 cDNA. Vaccination of naive mice either with this fusion DNA construct or with an OVA cDNA-containing plasmid protected the mice from the subsequent induction allergen-induced airway hyperresponsiveness (AHR). Moreover, vaccination of mice with preexisting AHR with the OVA-IL-18 fusion DNA, but not with the OVA cDNA plasmid, reversed established AHR, reduced allergen-specific IL-4, and increased allergen-specific IFN-gamma production (Maecker et al., 2001).
Molecule Role Annotation :
Administration of anti-IL-25 mAb during the sensitization phase of a mouse model of allergic airway disease resulted in significantly reduced levels of IL-5 and IL-13 production, eosinophil infiltration, goblet cell hyperplasia, and serum IgE secretion, and prevented allergenic hyper-responsiveness. Even more striking was the ability of anti-IL-25 mAb, administered only during the challenge phase of the response, specifically to prevent AHR even during an ongoing type 2 inflammatory response in the lungs (Ballantyne et al., 2007).
Molecule Role Annotation :
In this study, an anti-IL-33 antibody was evaluated against pulmonary inflammation in mice sensitized and challenged with ovalbumin. Treatment with anti-IL-33 significantly reduced serum IgE secretion, the numbers of eosinophils and lymphocytes, and concentrations of IL-4, IL-5, and IL-13 in bronchoalveolar lavage fluid compared with administration of a control antibody. Histological examination of lung tissue demonstrated that anti-IL-33 significantly inhibited allergen-induced lung eosinophilic inflammation and mucus hypersecretion. Our data demonstrate for the first time that anti-IL-33 antibody can prevent the development of asthma in a mouse model and indicate that blockade of IL-33 may be a new therapeutic strategy for allergic asthma (Liu et al., 2009).
Molecule Role Annotation :
The adjuvant and protective capacity against anaphylactic shock of the association between rough lipopolysaccharide of Brucella ovis (LPS) coencapsulated with ovalbumin (OVA), as a model allergen, in Gantrez AN nanoparticles was investigated. In a model of sensitized mice to OVA, the formulation with OVA and LPS-entrapped inside the nanoparticles administered intradermally in three doses of 3 microg of OVA each was the only treatment that totally protected the mice from death after a challenge with an intraperitoneal injection of OVA (Gómez et al., 2008).
Protein Note :
EF-hand, calcium binding motif; A diverse superfamily of calcium sensors and calcium signal modulators; most examples in this alignment model have 2 active canonical EF hands. Ca2+ binding induces a conformational change in the EF-hand motif, leading to...; cd00051
>CAA76887.1 p7 protein [Phleum pratense]
MADDMERIFKRFDTNGDGKISLSELTDALRTLGSTSADEVQRMMAEIDTDGDGFIDFNEFISFCNANPGL
MKDVAKVF
Molecule Role :
Protective antigen
Molecule Role Annotation :
The grass pollen allergen, Phl p 7, belongs to a family of highly cross-reactive calcium-binding pollen allergens. Because Phl p 7 contains most of the disease-eliciting epitopes of pollen-derived calcium-binding allergens, hypoallergenic variants were engineered according to the x-ray crystal structure of Phl p 7 for allergy vaccination. In three recombinant variants, amino acids essential for calcium binding were mutated, and two peptides comprising the N- and C-terminal half were obtained by synthetic peptide chemistry. Basophil histamine release and skin test experiments in allergic patients identified the peptides as the vaccine candidates with lowest allergenic activity. Immunization of rabbits with the peptides induced IgG Abs that blocked allergic patients' IgE binding to Phl p 7 and inhibited allergen-induced basophil degranulation (Westritschnig et al., 2004).
>CAA55390.1 Phl p I allergen [Phleum pratense]
MASSSSVLLVVVLFAVFLGSAYGIPKVPPGPNITATYGDKWLDAKSTWYGKPTGAGPKDNGGACGYKDVD
KPPFSGMTGCGNTPIFKSGRGCGSCFEIKCTKPEACSGEPVVVHITDDNEEPIAPYHFDLSGHAFGAMAK
KGDEQKLRSAGELELQFRRVKCKYPEGTKVTFHVEKGSNPNYLALLVKYVNGDGDVVAVDIKEKGKDKWI
ELKESWGAIWRIDTPDKLTGPFTVRYTTEGGTKTEAEDVIPEGWKADTSYESK
Molecule Role :
Protective antigen
Molecule Role Annotation :
On the basis of the experimentally determined B cell epitopes of Phl p 1, five synthetic peptides have been synthesized. These peptides are derived from the major Phl p 1 IgE epitopes and were between 28-32 amino acids long. When used as immunogens in mice and rabbits, the peptides induced protective IgG antibodies, which recognized the complete Phl p 1 wild-type allergen and group 1 allergens from other grass species. Moreover, peptide-induced antibodies inhibited the binding of grass pollen allergic patients IgE antibodies to the wild-type allergen (Focke et al., 2001).
>sp|O24650.1|PROF2_PHLPR RecName: Full=Profilin-2; AltName: Full=Allergen Phl p 11; AltName: Full=Pollen allergen Phl p 12; AltName: Full=Profilin 4; AltName: Allergen=Phl p 12
MSWQTYVDEHLMCEIEGHHLASAAILGHDGTVWAQSADFPQFKPEEITGIMKDFDEPGHLAPTGMFVAGA
KYMVIQGEPGAVIRGKKGAGGITIKKTGQALVVGIYDEPMTPGQCNMVVERLGDYLVEQGM
Molecule Role :
Protective antigen
Molecule Role Annotation :
The cDNA coding for timothy grass pollen profilin, Phl p 12, was used as a template to develop a new strategy for engineering an allergy vaccine with low IgE reactivity. Non-IgE-reactive fragments of Phl p 12 were identified by synthetic peptide chemistry and restructured (rs) as a new molecule, Phl p 12-rs. It comprised the C terminus of Phl p 12 at its N terminus and the Phl p 12 N terminus at its C terminus. Phl p 12-rs was expressed in Escherichia coli and purified to homogeneity. IgG Abs induced by immunization of mice and rabbits with Phl p 12-rs cross-reacted with pollen and food-derived profilins. Recombinant Phl p 12-rs, rPhl p 12-rs, induced less reaginic IgE to the wild-type allergen than rPhl p 12. However, the rPhl p 12-rs-induced IgGs inhibited allergic patients' IgE Ab binding to profilins to a similar degree as those induced by immunization with the wild type. Phl p 12-rs specific IgG inhibited profilin-induced basophil degranulation. In conclusion, a restructured recombinant vaccine was developed for the treatment of profilin-allergic patients (Westritschnig et al., 2007).
Molecule Role Annotation :
Study explored the role of intranasal delivery of T-bet on the differentiation of T(H) cell subsets and airway inflammation in the ovalbumin (OVA)-induced mouse model of allergic airway inflammation. Intranasal administration of AAV-T-bet efficiently balanced the T(H)1/T(H)2 transcription factor and cytokine profile and significantly decreased the number of eosinophils in BAL fluid. It also resulted in a reduction of peribronchial inflammation scores and serum IgE levels in OVA-sensitized and challenged mice during the effector phase, and inhibited airway inflammation during the challenge phase in a mouse model of allergic airway inflammation (Wang et al., 2008).
Molecule Role Annotation :
Researchers delivered either soluble mTACI-Ig (Tnfrsf13b) or anti-IgE to allergen-sensitized mice before airway challenge with allergen. Both mTACI-Ig and anti-IgE decreased the levels of total and allergen-specific IgE in the serum. Histopathologic analysis of lungs showed a reduction in disease severity scores for both treatment groups, but results were more pronounced in mTACI-Ig-treated mice. Neutrophil and eosinophil numbers in the bronchoalveolar lavage (BAL) were significantly reduced following mTACI-Ig treatment. Finally, mTACI-Ig treatment was more effective than anti-IgE treatment in reducing AHR to inhaled antigen (Bilsborough et al., 2008).
>NP_001070976.1 tumor necrosis factor receptor superfamily member 9 isoform 2 precursor [Mus musculus]
MGNNCYNVVVIVLLLVGCEKVGAVQNSCDNCQPGTFCRKYNPVCKSCPPSTFSSIGGQPNCNICRVCAGY
FRFKKFCSSTHNAECECIEGFHCLGPQCTRCEKDCRPGQELTKQGCKTCSLGTFNDQNGTGVCRPWTNCS
LDGRSVLKTGTTEKDVVCGPPVVSFSPSTTISVTPEGGPAFKKTTGAAQEEDACSCRCPQEEEGGGGGYE
L
Molecule Role :
Protective antigen
Molecule Role Annotation :
Using a murine asthma model, we show that a single injection of an anti-CD137 (Tnfrsf9, 4-1BB) mAb prevents the development of airway hyperreactivity, eosinophilic airway inflammation, excessive mucus production, and elevated IgE during the observation period of 7 weeks. Most importantly, even established disease is completely reversed by anti-CD137 mAb administration. These data demonstrate, for the first time to our knowledge, the capacity of anti-CD137 mAb to ameliorate allergic asthma (Polte et al., 2006).
III. Vaccine Information
1. Phleum pratense Allergy Phl p 12 Subunit Vaccine
A recombinant protein comprised of the C terminus of Phl p 12 at its N terminus and the Phl p 12 N terminus at its C terminus, Phl p 12-rs, was expressed in Escherichia coli and purified (Westritschnig et al., 2007).
Vaccination Protocol:
Mice were immunized s.c. with either 10 µg of rPhl p 12, 10 µg of rPhl p 12-rs, or a equimolar mixture of the five peptides (2 µg of each peptide) adsorbed to aluminum hydroxide (Westritschnig et al., 2007).
Immune Response:
rPhl p 12-rs induced IgG1 reactivity to rPhl p 12, rBet v 2, rCor a 2, and rDau c 4 that was of comparable magnitude as the reactivity induced by rPhl p 12 (Westritschnig et al., 2007).
Efficacy:
rPhl p 12-rs and the Phl p 12-derived peptides induced lower allergenic immune responses to the wild-type allergen than rPhl p 12 upon immunization of the mice and thus exhibited reduced in vivo allergenicity (Westritschnig et al., 2007).
IV. References
1. Ballantyne et al., 2007: Ballantyne SJ, Barlow JL, Jolin HE, Nath P, Williams AS, Chung KF, Sturton G, Wong SH, McKenzie AN. Blocking IL-25 prevents airway hyperresponsiveness in allergic asthma. The Journal of allergy and clinical immunology. 2007; 120(6); 1324-1331. [PubMed: 17889290].
2. Bilsborough et al., 2008: Bilsborough J, Chadwick E, Mudri S, Ye X, Henderson WR Jr, Waggie K, Hebb L, Shin J, Rixon M, Gross JA, Dillon SR. TACI-Ig prevents the development of airway hyperresponsiveness in a murine model of asthma. Clinical and experimental allergy : journal of the British Society for Allergy and Clinical Immunology. 2008; 38(12); 1959-1968. [PubMed: 19037968].
3. Chuang et al., 2006: Chuang YH, Suen JL, Chiang BL. Fas-ligand-expressing adenovirus-transfected dendritic cells decrease allergen-specific T cells and airway inflammation in a murine model of asthma. Journal of molecular medicine (Berlin, Germany). 2006; 84(7); 595-603. [PubMed: 16565865].
4. Edwan and Agrawal, 2007: Edwan JH, Agrawal DK. Flt3-ligand plasmid prevents the development of pathophysiological features of chronic asthma in a mouse model. Immunologic research. 2007; 37(2); 147-159. [PubMed: 17695249].
5. Eigenmann et al., 2008: Eigenmann PA, Asigbetse KE, Frossard CP. Avirulant Salmonella typhimurium strains prevent food allergy in mice. Clinical and experimental immunology. 2008; 151(3); 546-553. [PubMed: 18190606].
6. Focke et al., 2001: Focke M, Mahler V, Ball T, Sperr WR, Majlesi Y, Valent P, Kraft D, Valenta R. Nonanaphylactic synthetic peptides derived from B cell epitopes of the major grass pollen allergen, Phl p 1, for allergy vaccination. The FASEB journal : official publication of the Federation of American Societies for Experimental Biology. 2001; 15(11); 2042-2044. [PubMed: 11511525].
7. Gómez et al., 2008: Gómez S, Gamazo C, San Roman B, Ferrer M, Sanz ML, Espuelas S, Irache JM. Allergen immunotherapy with nanoparticles containing lipopolysaccharide from Brucella ovis. European journal of pharmaceutics and biopharmaceutics : official journal of Arbeitsgemeinschaft fur Pharmazeutische Verfahrenstechnik e.V. 2008; 70(3); 711-717. [PubMed: 18582571].
8. Keane-Myers et al., 1998: Keane-Myers AM, Gause WC, Finkelman FD, Xhou XD, Wills-Karp M. Development of murine allergic asthma is dependent upon B7-2 costimulation. Journal of immunology (Baltimore, Md. : 1950). 1998; 160(2); 1036-1043. [PubMed: 9551945].
9. Liu et al., 2009: Liu X, Li M, Wu Y, Zhou Y, Zeng L, Huang T. Anti-IL-33 antibody treatment inhibits airway inflammation in a murine model of allergic asthma. Biochemical and biophysical research communications. 2009; 386(1); 181-185. [PubMed: 19508862].
10. Maecker et al., 2001: Maecker HT, Hansen G, Walter DM, DeKruyff RH, Levy S, Umetsu DT. Vaccination with allergen-IL-18 fusion DNA protects against, and reverses established, airway hyperreactivity in a murine asthma model. Journal of immunology (Baltimore, Md. : 1950). 2001; 166(2); 959-965. [PubMed: 11145673].
11. Nagashima et al., 2008: Nagashima O, Harada N, Usui Y, Yamazaki T, Yagita H, Okumura K, Takahashi K, Akiba H. B7-H3 contributes to the development of pathogenic Th2 cells in a murine model of asthma. Journal of immunology (Baltimore, Md. : 1950). 2008; 181(6); 4062-4071. [PubMed: 18768862].
12. Peng et al., 2004: Peng HJ, Tsai LC, Su SN, Chang ZN, Shen HD, Chao PL, Kuo SW, Tsao IY, Hung MW. Comparison of different adjuvants of protein and DNA vaccination for the prophylaxis of IgE antibody formation. Vaccine. 2004; 22(5-6); 755-761. [PubMed: 14741169].
13. Polte et al., 2006: Polte T, Foell J, Werner C, Hoymann HG, Braun A, Burdach S, Mittler RS, Hansen G. CD137-mediated immunotherapy for allergic asthma. The Journal of clinical investigation. 2006; 116(4); 1025-1036. [PubMed: 16528411].
14. Simoes et al., 2008: Simoes DC, Vassilakopoulos T, Toumpanakis D, Petrochilou K, Roussos C, Papapetropoulos A. Angiopoietin-1 protects against airway inflammation and hyperreactivity in asthma. American journal of respiratory and critical care medicine. 2008; 177(12); 1314-1321. [PubMed: 18356565].
15. Wang et al., 2008: Wang SY, Yang M, Xu XP, Qiu GF, Ma J, Wang SJ, Huang XX, Xu HX. Intranasal delivery of T-bet modulates the profile of helper T cell immune responses in experimental asthma. Journal of investigational allergology & clinical immunology : official organ of the International Association of Asthmology (INTERASMA) and Sociedad Latinoamericana de Alergia e Inmunologia. 2008; 18(5); 357-365. [PubMed: 18973099].
16. Westritschnig et al., 2004: Westritschnig K, Focke M, Verdino P, Goessler W, Keller W, Twardosz A, Mari A, Horak F, Wiedermann U, Hartl A, Thalhamer J, Sperr WR, Valent P, Valenta R. Generation of an allergy vaccine by disruption of the three-dimensional structure of the cross-reactive calcium-binding allergen, Phl p 7. Journal of immunology (Baltimore, Md. : 1950). 2004; 172(9); 5684-5692. [PubMed: 15100313].
17. Westritschnig et al., 2007: Westritschnig K, Linhart B, Focke-Tejkl M, Pavkov T, Keller W, Ball T, Mari A, Hartl A, Stöcklinger A, Scheiblhofer S, Thalhamer J, Ferreira F, Vieths S, Vogel L, Böhm A, Valent P, Valenta R. A hypoallergenic vaccine obtained by tail-to-head restructuring of timothy grass pollen profilin, Phl p 12, for the treatment of cross-sensitization to profilin. Journal of immunology (Baltimore, Md. : 1950). 2007; 179(11); 7624-7634. [PubMed: 18025208].
