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Synthetic Peptides for Allergovacines

#3759


Allergovacines Based on Synthetic Peptides Imitating Т- and В-Cell Epitopes of Allergen

Tech Area / Field

  • CHE-SYN/Basic and Synthetic Chemistry/Chemistry
  • BIO-BCH/Biochemistry/Biotechnology and Life Sciences
  • BIO-IMU/Immunology/Biotechnology and Life Sciences

Status
3 Approved without Funding

Registration date
26.04.2007

Leading Institute
Institute of Immunological Engineering, Russia, Moscow reg., Lyubuchany

Supporting institutes

  • Institute of Immunology, Russia, Moscow

Collaborators

  • University of Turku / Finnish-Russian Joint Biotechnology Laboratory, Finland, Turku\nMcMaster University, Canada, ON, Hamilton\nReflab ApS, Denmark, Copenhagen\nImmunology Research Institute of New England, USA, MA, Fitchburg\nALLATRACT ltd Consultancy, UK, Pulborough\nVasogen Inc., Canada, ON, Mississauga

Project summary

The aim of the Project: to study a possibility for a construction of preparations for allergen-specific immunotherapy based on synthetic peptides imitating B-and B-cell epitopes of an allergen.

The Project is aimed for the study of a possibility to perform allergen-specific immunotherapy (ASIT) of atopic allergic diseases using preparations (complexes /conjugates) consisting of polymer nanoparticles and synthetic peptides imitating T- or B-cell epitops of the allergen. One of the widespread aeroallergens in the Central and Southern zones of Russia – allergen of timothy grass pollen (designation according to the International classification - G6) is supposed to be taken as a causative allergen. Peptides imitating T- and B-cell epitopes (TCE and BCE) of the major allergens of timothy grass pollen (Phl p1, Phl p5) will be obtained by chemical synthesis. The following polymeric nanoparticles (PNPs) will be obtained based on: 1) polylactide homopolymer; 2) co-polymer of polyethylene glycol and polylactide; 3) polybutycyanoacrylate; 4) polymethylmethacrylate. Nanoparticles will be complexed/conjugated with TCE and BCE with following evaluation of their efficacy and safety in the process of experimental ASIT using a model of IgE-dependent allergic asthma (IgE-AA) induced by timothy allergen(G6).

Construction of preparations for ASIT based on nanoparticles carrying TCE- and BCE- peptides will enable to update its safety, efficacy and standardization.

The stages of the work include structural analysis of T- and B-cellular epitopes of the major allergens of timothy grass pollen Phl p1, Phl p5, and synthesis of the corresponding peptides having reduced allergenicity and preserved immunogenicity.

Synthetic peptides will be studied in respect to their allergenicity and immunogenicity using in vivo and in vitro techniques. PNPs of necessay sizes will be synthesized, and evaluation of their physico-chemical properties will be performed. A complexing (conjugation) of the obtained TCE and BCE peptides with a suitable nano-carriers (PNPs) based on preliminary data of their adjuvant activity will be performed. Immunogenicity and allergenicity of the obtained preparations (complexes /conjugates of TCE and BCE peptidesof G6 with PNPs) in vivo and in vitro will be also studied. Experimental ASIT will be performed using a model of IgE-AA in mice induced with G6 allergen in order to find out the efficacy and safety of the obtained preparations regarding the the hyposensibilization of the organism.

All the Project participants have a sufficient experience in conducting of similar studies, as well as a backlog in the field of construction of complexed (conjugated) forms of allergens, modeling of IgE-AA in mice and performing of experimental ASIT, synthesis of allergenic peptides and PNPs.

As a result of the emplementation of the above research it is expected to obtain new data enabling a significant improvement of ASIT and to introduce them in clinical practice. A successful implementation of the Project will enable to start the production of allergovaccines of a new generation for ASIT based on peptide allergens and polymeric nano-carriers.

It is supposed to invite the Immunology Research Institute of New England (IRINE) (358, Elm Street, Gardner, MA 01440, USA), director Prof. Laurence М. Du Buske as a foreign collaborator.

Several studies are supposed to be performed at IRINE, particularly, in vitro studies of allergenicity of the obtained peptides using fiber optic technique of histamine detection, as well as holding of joint work meetings and symposia concerning the presentation of the results of the study on international conferences.


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