Analysis of the humoral response induced by Dengue and Zika virus infection using recombinant proteins from the envelope of these viruses

Abstract

The Flaviviridae are a family of RNA viruses transmitted by arthropods (mainly ticks and mosquitos) that may infect humans. All members of this family are part of the Flavivirus genus, being responsible for generalized morbidity and mortality all around the globe. Some of the mosquito-borne viruses cause diseases such as yellow fever, dengue fever, Japanese encephalitis, West Nile fever, and zika fever. In Brazil, we have the co-circulation of the yellow fever virus (YFV), for which there is already a very effective vaccine, and the dengue virus (DENV), which has circulated in the country for decades, causing many recent epidemics. More recently (probably around 2013) the zika virus (ZIKV) was introduced to the Brazilian population, where it was associated with the significant increase in cases of fetal microcephaly from newborns of infected mothers, and also severe neurological diseases such as Guillain-Barré Syndrome.The high similarity between ZIKV and DENV made most of the zika fever cases analyzed by the rapid IgM test for dengue to be considered false-positive. Considering that in Brazil the ZIKV circulates in DENV endemic areas, it is essential to analyze the humoral immune response against these viruses in order to detect possible candidates for a specific serological test or even for vaccines and treatments. Besides, DENV infection may be intensified by the ADE (Antibody-dependent enhancement) phenomenon, which predicts that a secondary infection by a different DENV serotype may be increased if the subject has been previously infected. This happens due to the presence of antibodies against the primary infection that may cross-react, but not neutralize the secondary infection. In this context, it becomes important to know if previous immunity to DENV is capable to increase the infection by ZIKV.For these reasons, we are interested in analyzing in detail the humoral immune response of patients previously infected with DENV or ZIKV. To do so, we will express a panel of recombinant envelope (E) proteins from the 4 DENV serotypes and their domains: domain I/II (EDI/II) and domain III (EDIII). The ZIKV proteins will be produced in a collaborative study with "Laboratório de Vacinas Experimentais at UNIFESP". With this panel of proteins, we will be able to analyze the cross-reactivity of the patient's sera, seeking to understand how the humoral immune response of previously infected patients develops for each virus. (AU)