| Grant number: | 05/04514-2 |
| Support Opportunities: | Regular Research Grants |
| Start date: | August 01, 2006 |
| End date: | May 31, 2009 |
| Field of knowledge: | Biological Sciences - Biochemistry - Chemistry of Macromolecules |
| Principal Investigator: | Maria Helena Bueno da Costa |
| Grantee: | Maria Helena Bueno da Costa |
| Host Institution: | Instituto Butantan. Secretaria da Saúde (São Paulo - Estado). São Paulo , SP, Brazil |
Abstract
Arthropod bites and stings are capable of inflicting injury, inciting allergic reactions, and transmitting systemic disease. Members of the Hymenoptera order are of particular importance because they are nearly ubiquitous in nature1-5, and their stings may cause life-threatening allergic reactions6. Stings from bees, wasps, and ants produce a variety of clinical and histological manifestations. Anaphylaxis following an insect sting is the most serious complication. For individuals with a specific allergy to Hymenoptera venom, the venom immunotherapy (VIT) may be a relatively effective treatment option7. Treatments failures do however occur and VIT may cause frequent systemic allergic side effects, mainly in honeybee venom allergy persons7, 8. The Immunotherapy is expensive and time consuming8. New strategies to improve safety and efficacy of this treatment are therefore of general interest7. We propose here a systematic approach to study the basic and biotechnological problems related with the development of safe formulations of bee venoms within liposomes to be used in VIT. We intend to start studying the mainly molecular characteristics related to mellitin/lipid interactions. It is known, that mellitin (Mel) is the major toxic peptide in the European honey bee venom (50 % of the wet weight) and that it has a powerful haemolytic activity and it is responsible for local pain. The biotechnological challenge here is to chemically modify the mellitin molecule to permit its encapsulation within liposomes. The Mel biological toxicity will, probable, decrease by two reasons: 1. because the molecule will possibly lose its haemorrhagic activity through chemical modification and 2. the lipossomal encapsulation will avoid direct contact between Mel and the organism and, in addition, this vehicle has adjuvant characteristics. As a direct consequence it will be possible, in the future, to design a formulation for preventive (VIT) and/or curative medicines (a bee venom component as an anti arthritic drug, for example).The idea is to work with the bee venom components mellitin and phospholipase. Here, in this first project, we will work with the mellitin.When analysed together, these literature data, lead us to formulate and fundament our propositions: 1. To chemically modify the W of Mel to impeach or to minimize the peptide/membrane interaction.2. To encapsulate the W-Mel modified molecule within membrane rich cholesterol.In addition,3. To chemically modify the Mel NH2 terminus Lys 7, 21 and 23.We strongly believe that the modified molecule will be non toxic and its immunogenicity will be retained. The encapsulation of the modified Mel within liposome will be a formulation containing adjuvant and so we expect that less quantities of the antigen will be required to obtain the same benefits in venom immunotherapy.These assumptions must be detailed at molecular level to designing an intelligent formulation. (AU)
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