Banca de DEFESA: ANTÔNIO MÁRCIO SANTANA FERNANDES

Uma banca de DEFESA de DOUTORADO foi cadastrada pelo programa.
STUDENT : ANTÔNIO MÁRCIO SANTANA FERNANDES
DATE: 07/07/2022
TIME: 09:00
LOCAL: SALA DA PLATAFORMA DE CONFERÊNCIA WEB RNP
TITLE:

Development of a multicomponent hypoallergen of t-cell epitopes of the allergens Der p 1, Der
p 2 and Der p 23 and its potential use in the treatment of allergy to the mite Dermatophagoides
pteronyssinus

KEY WORDS:

House dust mite, hypoallergen, immunogenicity, vaccine candidate, allergen immunotherapy

PAGES: 100
BIG AREA: Outra
AREA: Tecnologia e Inovação
SUMMARY:

Introduction: Exposure to house dust mites, such as Dermatophagoides pteronyssinus, triggers
reactions that stimulate and induce the pathophysiology of allergic asthma. Allergen-specific
immunotherapy (AIT) is the only treatment capable of inducing tolerance to allergens and the
only alternative to current pharmacological treatment, which has several side effects. Although
some AIT protocols are performed using crude extracts, bringing some limitations, new
approaches aim at the construction of hybrid hypoallergens of T cell epitopes. These constructs
can be produced in order to increase immunogenicity, reducing the number of molecules that
need to be produced to be included in a vaccine formulation. Objective: To produce a
hypoallergenic hybrid protein based on the main allergens of the dust mite D. pteronyssinus for
use in immunotherapy in allergic diseases caused by this mite. Methods: Hybrid hypoallergen
rDer p 2231, designed using dominant sequences of antigenic regions of T cell epitopes of Der
p 1, Der p 2 and Der p 23 allergens and purified by affinity chromatography, had its reactivity
to human IgE verified in comparison with parental allergens. A total of 18 cytokines were
evaluated in the supernatant of PBMCs from atopic and non-atopic individuals, stimulated with
rDer p 2231. The therapeutic potential of the hybrid rDer p 2231 was also evaluated through
the acute and chronic murine models of D. pteronyssinus mite allergy. . Results: The rDer p
2231 hybrid stimulated in PBMCs isolated from atopic patients and from splenocytes of mice
treated with rDer p 2231, higher levels of Th1 profile cytokines and regulatory cytokines, as
well as lower levels of Th2 profile cytokines. The use of hybrid molecules as a therapeutic
model in mice allergic to D. pteronyssinus led to reduced IgE production and lower eosinophilic
peroxidase activity in the airways. In addition to these findings, rDer p 2231 acts in the chronic
model of allergy, significantly reducing smooth muscle hypertrophy, decreased subbasal
membrane fibrosis, goblet cell hyperplasia and allergic inflammatory response, such as airway
hyperreactivity. Conclusion: rDer p 2231 is a multicomponent hybrid molecule with potential
to be used in TIA in patients co-sensitized to major D. pteronyssinus allergens, since it was able
to reduce IgE production, inducing allergen-specific blocking antibodies, restoring and
balancing Th1/Th2 responses and induction of regulatory T cells, in addition to reducing the
tissue pathological effects associated with chronic asthma.

BANKING MEMBERS:
Presidente - 1927897 - CARINA DA SILVA PINHEIRO
Externo à Instituição - LEONARDO AUGUSTO DE ALMEIDA
Externa ao Programa - 2584365 - LUCIANA SANTOS CARDOSO
Interno - 1561789 - RICARDO WAGNER DIAS PORTELA
Externa ao Programa - 1090486 - SILVANA BEUTINGER MARCHIORO