Abstract
BackgroundThe arboviruses Zika virus (ZIKV) and Dengue virus (DENV) have important epidemiological impact in Brazil and other tropical regions of the world. Recently, it was shown that previous humoral immunity to DENV enhances ZIKV replication in vitro, which may lead to more severe forms of the disease. Thus, traditional approaches of vaccine development aiming to control viral infection through neutralizing antibodies may induce cross-reactive enhancing antibodies. In contrast, cellular immune response was shown to be capable of controlling DENV infection independently of antibodies. The aim of the present study was to design a flavivirus NS5 protein capable of inducing a cellular immune response against DENV and ZIKV.MethodsA consensus sequence of ZIKV NS5 protein was designed among isolates from various continents. Epitopes were predicted for the most prevalent alleles of class I and II HLA in the Brazilian population. Then, this epitopes were analyzed with regard to their conservation, population coverage and distribution along the whole antigen.ResultsNineteen epitopes predicted to be more reactive (percentile rank <1) and 100% conserved among ZIKV and DENV serotypes were selected. The distribution of such epitopes along the protein was shown on a three-dimensional model and population coverage was calculated for different regions of the world. The designed protein was predicted to be stable and the distribution of selected epitopes was shown to be homogeneous along domains. The population coverage of selected epitopes was higher than 50% for most of tropical areas of the world.ConclusionSuch results indicate that the proposed antigen has the potential to induce protective cellular immune response to ZIKV and DENV in different human populations of the world.
Highlights
The arboviruses Zika virus (ZIKV) and Dengue virus (DENV) have important epidemiological impact in Brazil and other tropical regions of the world
ZIKV non-structural protein 5 (NS5) phylogeny In order to verify the origin of ZIKV isolates from Brazil and the Americas we carried out a phylogenetic analysis with NS5 amino acid sequences from ZIKV from throughout the world
We included NS5 sequences from DENV serotypes from different genotypes isolated in different continents in order to verify similarities among ZIKV and DENV proteins
Summary
The arboviruses Zika virus (ZIKV) and Dengue virus (DENV) have important epidemiological impact in Brazil and other tropical regions of the world. The only anti-DENV vaccine candidate approved for use in humans is based on a chimera between DENV and Yellow fever virus (YFV) [6,7,8,9,10] It consists of chimeric viruses for each of DENV serotypes in which dos Santos Franco et al Journal of Biomedical Science (2017) 24:88 genomic sequences coding for YFV envelope proteins were replaced by those of DENV. Some severe forms of dengue are mediated by a phenomenon called antibody-dependent enhancement, in which immunoglobulins produced in response to a previous DENV serotype cross-react with viral particles of a second serotype and mediate enhanced infection of Fc-γ receptor bearing cells. Such enhanced infection leads to higher viral loads and severe disease. The risk of inducing antibody-mediated enhancement of infection between these two major arboviruses will depend on the profile of immune response induced
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