Banca de QUALIFICAÇÃO: CÁSSIO RICARDO DE MEDEIROS SOUZA

Uma banca de QUALIFICAÇÃO de DOUTORADO foi cadastrada pelo programa.
STUDENT : CÁSSIO RICARDO DE MEDEIROS SOUZA
DATE: 28/12/2020
TIME: 09:00
LOCAL: Videoconferência
TITLE:

A STUDY OF ZIKV SEROLOGICAL DIAGNOSIS EFFICACY IN GUILLAIN-BARRÉ SYNDROME AND ANTI-ZIKV ANTIBODIES RESPONSE IN CONGENITAL ZIKV SYNDROME CASES

KEY WORDS:

ZIKV; serological diagnosis; IgG3; GBS; long-therm anti-NS1 antibodies; long therm anti-ZIKV neutralizing antibodies; CZS.

PAGES: 119
BIG AREA: Ciências Biológicas
AREA: Bioquímica
SUMMARY:

Between 2015 and 2016, Brazil experienced the biggest ZIKV epidemic ever recorded, which has become a public health problem not only due to the large number of cases, but mainly due to the emergence of other more serious clinical conditions associated with infection, such as Guillain-Barré Syndrome (SGB) and ZIKV Congenital Syndrome (SCZ). The study of the efficacy of the serological diagnosis and the antibody response profile are two big questions in the context of ZIKV infection. The serological diagnosis is made through the detection of anti-NS1 antibodies, but there is evidence of cross-reactivity with other flaviviruses, impairing the specific diagnosis of ZIKV infection. It is also important to study the kinetics and profile of anti-ZIKV antibodies after infection, in order to determine their duration and protection capacity through a new exposure, allowing a better understanding
of the population's response to a new epidemic. This thesis, therefore, addresses these two issues in two separate chapters. In Chapter I, we assessed the efficacy of NS1-based serology in the differential diagnosis of previous ZIKV infection in cases of GBS. The ROC analysis demonstrated that NS1-based ELISA for detection of IgM and total IgG antibodies showed specificity of 18.75% (AUC 0.6203, p = 0.061) and 58.87% (AUC 0.7351, p <0,
0001), respectively, not being considered effective enough to ensure a reliable diagnosis. The ELISA for detection of total IgG showed better performance and was used to detect anti-NS1 antibodies in samples from 152 patients who developed GBS between 2009 and 2018. It was possible to observe a high rate of positivity in samples dating from 2015 (92.6% of the total), the year which epidemic started, with statistical difference when compared with previous (p = 0.0027 for 2013 and p = 0.0168 for 2014) and
later years (p <0.0001 for 2017). The results suggest that, despite not having desirable specificity, the test has sufficient sensitivity to show recent exposure to ZIKV. The ELISA for detection of anti-ZIKV IgG3 showed a specificity of 85.42% (AUC 0.6203, p = 0.0274), being considered more effective to diagnose previous ZIKV infection cases. Together, the serological results obtained allow the identification of signs of recent ZIKV infection in 38.6% of patients who developed GBS during the ZIKV epidemic between 2015 and 2016. In Chapter II, we evaluated the response profile of biomarker and anti-ZIKV neutralizing antibodies in mothers who gave birth to healthy (C-) and SCZ-affected children, in order to determine the difference in response between these groups, the permanence of these antibodies in the circulation and whether they are able to confer protection against a new ZIKV exposure. Using an NS1-based ELISA, we detected a lower positivity rate for total IgG anti-ZIKV in C- mothers (33.3%) than in SCZ mothers (64.3%)  evaluated between 8 and 24 months postpartum (mpp), with statistically significant difference between groups (p = 0.0202). Among mothers evaluated between 25 and 44 mpp, positivity of 36.4% was observed in the C- group and 35.3% in the SCZ group, with no statistical difference between the groups (p = 0.7756). The data indicate that it is possible to identify antibodies markers of ZIKV infection by up to 24 mpp, but there is no permanence of these antibodies for later periods. The positivity rate for neutralizing antibodies detected by plaque reduction neutralization test (PRNT) among SCZ mothers evaluated between 8 and 24 mpp was 92.3%, while C- mother samples evaluated in the same period did not show any anti-ZIKV neutralizing activity (p <0.0001, when comparing the two groups). The presence of neutralizing antibodies in SCZ mothers indicates that there is a protective response of up to 24 mpp, in addition to providing evidence of previous exposure to ZIKV. The correlation analysis between the results obtained for anti-NS1 and neutralizing antibodies showed that there is no association between the variables (r = 0.3680, p = 0.1211), suggesting that the neutralizing activity is not conferred by anti-NS1 antibodies. Further studies are needed to better characterize the role of IgG3 antibodies as more specific biomarkers of recent ZIKV infection in patients who have developed GBS and of long-therm anti-NS1 antibodies as markers of previous ZIKV exposure in mothers who gave birth children with SCZ, as well as protection against new exposures by neutralizing anti-ZIKV antibodies.

BANKING MEMBERS:
Interna - 1549705 - ADRIANA FERREIRA UCHOA
Externa ao Programa - 1714243 - DANIELLA REGINA ARANTES MARTINS SALHA
Presidente - 1046922 - LEONARDO CAPISTRANO FERREIRA