Banca de DEFESA: FERNANDA MARIA LESSA CARVALHO

Uma banca de DEFESA de MESTRADO foi cadastrada pelo programa.
STUDENT : FERNANDA MARIA LESSA CARVALHO
DATE: 21/07/2022
TIME: 09:00
LOCAL: IGM Sala Virtual 3
TITLE:

Identification of epitopes associated with resistance to Schistosoma mansoni infection in individuals from an endemic area after treatment with praziquantel.

KEY WORDS:

Schistosoma mansoni; Peptide microarray; Vaccine; Resistance/protection

PAGES: 86
BIG AREA: Ciências Biológicas
AREA: Farmacologia
SUMMARY:

ABSTRACT
INTRODUCTION: The production of a vaccine against schistosomiasis would be a valuable
addition to the measures currently in use to control and, ultimately, eradicate this disease.
However, no vaccine formulation has advanced to the final stage of development. The first
initiatives were based on the use of unique antigens that were very immunogenic, but with
cytosolic or cytoskeletal localization, therefore not exposed in live. Recently, efforts have
evaluated targets at the host-parasite interface, however always as unique targets, a strategy not
effective for such a complex parasite. In this context, we advocate the use of multiple
immunogenic epitopes, located at the parasite-host interface and associated with a protective
response against schistosomes. Endemic area studies showed changes in antibody levels and
classes after treatment with Praziquantel (PZQ), which are associated with resistance to
reinfection (RR). This phenomenon is known as “drug-induced resistance”. Our working
hypothesis is that it would be possible to explore the response in these individuals in order to
identify epitopes associated with resistance for the rational design of a schistosoma vaccine.
OBJECTIVES: Pinpoint protein epitopes recognized by the serum of individuals RR to S.
mansoni from an endemic region of Bahia. METHODS: To identify the epitopes, we
performed peptide microarray assays containing 59 proteins of interest using the serum of
individuals from an endemic area for schistosomiasis (Conde-BA), selected by their history of
resistance (RR) or susceptibility (SR) to S. mansoni reinfection after PZQ therapy. Subjects
were followed up for 18 months after PZQ treatment, with sampling of serum for ELISA (IgG1,
IgG4 and IgE) and stool for Kato-Katz at 0, 1, 6, 12, 18 months. RESULTS: The RR
individuals presented higher levels of IgG1 antibodies against tegument membranes (SmTeg),
as well as total IgE and specific IgE against soluble proteins of adult worms (SWAP). Two
tegument targets (Sm25 and ADP-Ribosyl Cyclase) revealed epitopes preferentially recognized
by the serum of RR individuals. Epitopes with higher reactivity in SR individuals were
identified in the MEG-12 and MEG-4.1 proteins of the esophageal gland. CONCLUSION:
Despite the variation in epitope recognition and targets shared between groups (RR and SR),
humans resistant to S. mansoni reinfection preferentially recognize epitopes in proteins (Sm25
and ADP-Ribosyl cyclase). Additionally, the antibody titer presented by the subject appears to
be as important as the nature of the target protein to mount an effective response against the
worm.

BANKING MEMBERS:
Externa à Instituição - CRISTINA TOSCANA FONSECA - FIOCRUZ-MG
Interna - 2573399 - DEBORAH BITTENCOURT MOTHE FRAGA
Presidente - 249.563.328-58 - LEONARDO PAIVA FARIAS - USP