Anticorpos anti-flaviviridae nas síndromes de Guillain-Barré e congênita associada à infecção pelo vírus Zika

Abstract

Between 2015 and 2016, Brazil experienced the major epidemics of Zika virus (ZIKV) registered until now, which became a public health problem not only because the number of cases, but mainly by the onset of critical infection-associated clinical conditions, like Guillain-Barré (GBS) and Congenital Zika Syndromes (CZS). The evaluation of serological diagnosis efficacy and antibody response profile are two great issues in ZIKV infection. Serological diagnosis is mainly performed by detection of antiNS1 antibodies, but there is evidence about cross-reactivity with antibodies against other flaviviruses, which impairs the ZIKV infection specific diagnosis. It is of importance the study anti-ZIKV antibody responses and their kinetics post-infection, to determine the existence of long-term antibodies and its protective capacity. So, the present work focused in these two goals. First, to determine the efficacy NS1-based serology to detect anti-ZIKV IgM, total IgG and IgG3 and anti-DENV and its application in determining prior ZIKV infection prior to GBS onset. The presence of anti-ZIKV and anti-DENV antibodies in patients who developed GBS between 2009 and 2018, residents of DENV endemic area, was registered. The presence of these antibodies in individuals who developed GBS before ZIKV introduction indicates the occurrence of cross-reactivity between anti-flaviviridae antibodies. Data indicates that IgM and total IgG serology, although with considerable sensitivity, do not present specificity enough to supports differential diagnosis of ZIKV infection. However, anti-NS1 IgG3 serology shows better performance, making possible the identification of ZIKV-associated GBS cases with more efficacy. Next, the presence of anti-NS1, anti-E and neutralizing antibodies against ZIKV and/or DENV, was determined in woman who gave birth to children with CZS; they were evaluated in two distinct periods, 8-24 months postpartum and 25-44 months post-partum, aiming to identify the occurrence of long-term protective antibody response. The results indicate significant presence of anti-NS1, anti-E and neutralizing antibodies in woman evaluated between 8- and 24-months post-partum, as sign of previous ZIKV exposition. In the second group, it was not possible to identify significant presence of anti-NS1 and anti-E antibodies, suggesting time-associated decay of the response. However, the presence of neutralizing antibodies was registered. Anti-ZIKV neutralizing response are related to the presence of anti-ZIKV antibodies in the first group and, in the second one, this phenomenon was associated with the occurrence of anti-DENV antibodies, suggesting cross-protective activity between anti-ZIKV and anti-DENV antibodies. As a conclusion, more studies are mandatory not only to allow a better characterization of IgG3 role as specific markers of ZIKV infection, and long-term anti-NS1 and anti-E as anti-ZIKV neutralizing antibodies, but also to improve serological diagnosis strategies and enforces the knowledge about kinetics and protective role of anti-ZIKV antibodies.