Modulation of Antigen-specific antibody production to Polybia paulista venom and mastocyte activation in mouse experimental model of allergy: effects of bystander suppression induced by oral tolerance to uncorrelated protein antigens

• Grant number: 19/22024-5
• Support Opportunities: Scholarships in Brazil - Scientific Initiation
• Start date: August 01, 2020
• End date: March 31, 2021
• Field of knowledge: Health Sciences - Medicine - Medical Clinics
• Principal Investigator: Luis Gustavo Romani Fernandes
• Grantee: Leonardo Antonio Benedito Mainente
• Host Institution: Faculdade de Ciências Médicas (FCM). Universidade Estadual de Campinas (UNICAMP). Campinas , SP, Brazil

Abstract

Allergen-specific immunotherapy (AIT) is the only treatment with long-term effects, indicated for serious cases with risk of death due to anaphylaxis. However, AIT is ineffective in the treatment of multi-sensitized patients and could trigger intense adverse reactions for some types of allergens, mainly during the induction period and preliminary phases of maintenance of immunotherapy. To overcome these difficulties, the use of oral tolerance induction protocols with uncorrelated protein antigens can be a useful strategy. In this context, these antigens may induce mechanisms of peripheral tolerance, capable of suppressing the immune responses directed also to other antigens present nearby, a phenomenon known as bystander suppression. The present work aims to evaluate the immunomodulatory mechanisms, related to the bystander suppression in experimental mouse model of allergy to Polybia paulista (P. paulista) wasp venom. To this, oral tolerance induction protocols with the ovalbumin protein antigen (OVA) will be tested in BALB/c mice, which will be previously sensitized with P. paulista wasp venom antigens, and in mice that will be sensitized immediately after oral tolerance induction. In these experimental models, the humoral and cellular immune responses specific to OVA and to P. paulista venom protein antigens will be evaluated. For this purpose, the profile of antigen-specific immunoglobulins (sIgE, sIgG1 and sIgG2a) and the quantification of the protease derived from the activation of MCP-1 mast cells will be evaluated in serum samples. Understanding the immunomodulatory mechanisms involved in the bystander suppression phenomenon on the production of different antigen-specific antibody classes and subclasses, as well as the mast cell activation profile, may provide support to the development of more effective IAE protocols.