Banca de DEFESA: Karen Stephanie de Souza Mangabeira

Uma banca de DEFESA de MESTRADO foi cadastrada pelo programa.
STUDENT : Karen Stephanie de Souza Mangabeira
DATE: 17/11/2023
TIME: 14:00
LOCAL: Auditório 03 do Instituto de Biologia
TITLE:

"DNA vaccine prototypes for Chagas disease: proof of concept and immunogenicity of Trypanosoma cruzi proteases".

KEY WORDS:

Chagas disease; Vaccines; mRNA; DNA; Proteases; Thimet oligopeptidase; Prolyl oligopeptidase.

PAGES: 120
BIG AREA: Ciências Biológicas
AREA: Imunologia
SUBÁREA: Imunologia Aplicada
SUMMARY:

Chagas Disease (CD) poses a significant public health challenge, primarily in endemic regions of Latin America and other affected areas. This disease, caused by the parasite Trypanosoma cruzi, is primarily transmitted by vector insects commonly known as "kissing bugs." However, transmission can also occur through oral ingestion, blood transfusions, organ transplantation, and congenital transmission. CD is characterized by an acute phase, which can be asymptomatic or present mild and nonspecific symptoms, followed by a chronic phase that primarily affects the heart and digestive system. Effective treatment for Chagas Disease is a challenge because available options are limited and often associated with side effects. Moreover, early diagnosis is crucial, as many patients do not exhibit symptoms in the initial phase. The lack of effective treatments and the need for prevention have spurred efforts to develop vaccines capable of protecting against the parasite. In this study, we focused our efforts on investigating two T. cruzi proteases, Prolyl Oligopeptidase (POPTc80) and Thimet Oligopeptidase (TOP), which play a role in the parasite's life cycle and represent potential vaccine targets. We explored three distinct approaches for developing vaccine prototypes: recombinant proteins, DNA vaccines, and mRNA vaccines. Recombinant proteins were produced in Escherichia coli, and we developed an optimized vector for mRNA production, which proved effective in expressing antigens in mice. Furthermore, we evaluated different routes of administration, with the intramuscular route being the most suitable due to its ability to maintain antigen expression over an extended period. However, our efforts to develop oral immunization formulations using sodium alginate were unsuccessful, highlighting the specific challenges associated with this administration route. In summary, CD is a challenging illness that lacks effective treatments and early diagnosis. Our research efforts seek innovative approaches to develop vaccines aimed at preventing Trypanosoma cruzi infection. Understanding the immune response mechanisms triggered by the studied proteases is essential to advance toward more effective vaccines against this neglected disease.

COMMITTEE MEMBERS:
Presidente - 2492352 - IZABELA MARQUES DOURADO BASTOS CHARNEAU
Interna - 1208515 - ANDREA QUEIROZ MARANHAO
Externo ao Programa - 1876284 - VICENTE DE PAULO MARTINS - UnBExterna à Instituição - LIVIA PIMENTEL DE SANT ANA DOURADO - UNIEURO