Evaluation of the potential use of hypoallergenic variants derived from the Poly p 1 and Poly p 5 allergens of the Polybia paulista wasp venom in protocols of allergen-specific immunotherapy

• Grant number: 24/23516-7
• Support Opportunities: Regular Research Grants
• Start date: May 01, 2025
• End date: April 30, 2028
• Field of knowledge: Health Sciences - Medicine - Medical Clinics
• Principal Investigator: Luis Gustavo Romani Fernandes
• Grantee: Luis Gustavo Romani Fernandes
• Host Institution: Faculdade de Ciências Médicas (FCM). Universidade Estadual de Campinas (UNICAMP). Campinas , SP, Brazil
• Associated researchers: Marcos Vinicius de Sousa ; Marilda Mazzali ; Mario Sergio Palma

Abstract

Hymenoptera stings can have potentially fatal effects as a result of poisoning and anaphylactic reactions, with the kidneys being one of the organs most affected in accidents involving multiple stings. Allergy to the protein components of hymenoptera venoms (allergens) is one of the three main causes of anaphylaxis in the world. However, the only intervention currently available capable of modifying the biological response to these allergens is the use of these insects' own venom in immunotherapy protocols (VIT). The Polybia paulista wasp is a species found in urban areas, mainly in the state of São Paulo. Phospholipase A1 (Poly p 1), hyaluronidase (Poly p 2) and antigen 5 (Poly p 5) have been identified as the three main allergens in the venom of this species that are recognized by specific immunoglobulin E (sIgE) in patients allergic to components of wasp venom. The heterologous expression of wild forms or hypoallergenic variants (HVs) of these allergens could be a potential source of biotechnological immunotherapeutic products for the development of new VIT protocols. In this context, the main objective of this project is to evaluate the potential use of VHs derived from the Poly p 1 and Poly p 5 allergens of the P. paulista wasp venom in allergen-specific immunotherapy protocols. For this purpose, HVs will be obtained by targeted mutagenesis of the sequences of the regions encoding the main linear B-cell epitopes of the recombinant allergens rPoly p 1 and rPoly p 5 and expressed in insect cell line. Initially, the VH will be evaluated for their ability to be recognized by sIgE from allergic patients and animals immunized with P. paulista venom, as well as their functional ability to mediate activation responses of basophils sensitized with sIgE. In mouse experimental models of sensitization to P. paulista venom, we will evaluate: 1- the immune reactivity profile after challenge with VHs (production of sIgs and mediators released by activated mast cells), 2 - the ability of VHs to induce anaphylaxis ("scoring" and measurement of body temperature), 3 - renal toxicity after multiple injections with VHs (evaluation of acute renal injury) and 4 - the ability to modulate humoral (production of sIgs and mast cell activation factors) and cellular immune responses (phenotypic/functional profile of TCD4+ lymphocytes) in animals submitted to VIT protocols with VHs. In this sense, we believe that the relevance of this proposal will support the development of new clinical VIT protocols with the generation of patentable immunotherapeutic products for the treatment of allergy to Hymenoptera venoms. (AU)