Abstract:Dengue is currently one of the most important arbovirus infections worldwide. Early diagnosis is important for disease outcome, particularly for those afflicted with the severe forms of infection. The goal of this work was to identify conserved and polymorphic linear B-cell Dengue virus (DENV) epitopes that could be used for diagnostic purposes. To this end, we aligned the predicted viral proteome of the four DENV serotype and performed in silico B-cell epitope mapping. We developed a script in Perl integratin… Show more
“…Pérez-Olmeda [17] evaluates the performance characteristics of the LIAISON XL Zika Capture IgM II. Versiane et al [18] describe the identification of B-cell epitopes with potential use to discriminate dengue from zika infections in serological assays.…”
“…Pérez-Olmeda [17] evaluates the performance characteristics of the LIAISON XL Zika Capture IgM II. Versiane et al [18] describe the identification of B-cell epitopes with potential use to discriminate dengue from zika infections in serological assays.…”
“…In this regard, extensive analysis has been performed on the characterization of immunodominant epitopes present in the flavivirus structural proteins Capsid, prM and Envelope and the non-structural protein NS1, which are main targets of the humoral immune response (19). Important epitopes present in the other non-structural proteins have also been described to be targeted by Abs (22,34) and they represent potential Ags to be used in immunoassays. The peptides evaluated in this work span the entire DENV proteome and they were based on their ability to be recognized by Abs present in the serum from DENV infected individuals (22).…”
In a world with an increasing population at risk of exposure to arthropod-borne flaviviruses, access to timely and accurate diagnostic tests would impact profoundly on the management of cases. Twenty peptides previously identified using a flavivirus proteome-wide microarray were evaluated to determine their discriminatory potential to detect dengue virus (DENV) infection. This included nine peptides recognized by IgM antibodies (PM peptides) and 11 peptides recognized by IgG antibodies (PG peptides). A bead-based multiplex peptide immunoassay (MPIA) using the Luminex technology was set-up to determine Ab binding levels to each of these peptides in a panel of 323 carefully selected human serum samples. Sera are derived from individuals either infected with different viruses, namely, the four DENV serotypes, Zika virus (ZIKV), yellow fever virus (YFV), chikungunya virus (CHIKV), West Nile virus (WNV) and Human immunodeficiency virus (HIV), or receiving vaccination against YFV, tick-borne encephalitis (TBEV), and Japanese encephalitis virus (JEV). Additionally, a set of healthy controls were included. We targeted a minimum specificity of 80% for all the analysis. The PG-9 peptide had the best sensitivity (73%) when testing DENV sera from acute patients (A-DENV; <8 days since symptom onset). With sera from convalescent DENV patients (C-DENV; >10 days since symptom onset) the FPG-1 peptide was the best seromarker with a sensitivity of 86%. When combining all A-DENV and C-DENV samples, peptides PM-22 and FPG-1 had the best-diagnostic performance with a sensitivity of 60 and 61.1%, and areas under the curve (AUC) of 0.7865 and 0.8131, respectively. A Random forest (RF) algorithm was used to select the best combination of peptides to classify DENV infection at a targeted specificity >80%. The best RF model for PM peptides that included A-DENV and C-DENV samples, reached a sensitivity of 72.3%, while for PG peptides, the best RF models for A-DENV only, C-DENV only and A-DENV + C-DENV reached a sensitivity of 88.9%, 89.1%, and 88.3%, respectively. In conclusion, the combination of multiple peptides constitutes a founding set of seromarkers for the discrimination of DENV infected individuals from other flavivirus infections.
“…Furthermore, in order to quickly diagnose all dengue virus serotypes and avoid cross-reactions between the crude DENV extracts and other flaviviruses, a tetra-epitope peptide that selected one to four serotypes from E protein within the DENV was expressed by a plant expression system, with a sensitivity of 71.7% and specificity of 100% [ 106 ]. Moreover, another important result observed was the capturing of a conserved peptide that has the latent capacity to recognize all four DENV serotypes and distinguish them from Zika virus-positive serotype [ 114 ]. Thus, it is clear that the epitope has extraordinary prospects in the diagnosis of DENV.…”
Infectious diseases, caused by various pathogens in the clinic, threaten the safety of human life, are harmful to physical and mental health, and also increase economic burdens on society. Infections are a complex mechanism of interaction between pathogenic microorganisms and their host. Identification of the causative agent of the infection is vital for the diagnosis and treatment of diseases. Etiological laboratory diagnostic tests are therefore essential to identify pathogens. However, due to its rapidity and automation, the serological diagnostic test is among the methods of great significance for the diagnosis of infections with the basis of detecting antigens or antibodies in body fluids clinically. Epitopes, as a special chemical group that determines the specificity of antigens and the basic unit of inducing immune responses, play an important role in the study of immune responses. Identifying the epitopes of a pathogen may contribute to the development of a vaccine to prevent disease, the diagnosis of the corresponding disease, and the determination of different stages of the disease. Moreover, both the preparation of neutralizing antibodies based on useful epitopes and the assembly of several associated epitopes can be used in the treatment of disease. Epitopes can be divided into B cell epitopes and T cell epitopes; B cell epitopes stimulate the body to produce antibodies and are therefore commonly used as targets for the design of serological diagnostic experiments. Meanwhile, epitopes can fall into two possible categories: linear and conformational. This article reviews the role of B cell epitopes in the clinical diagnosis of infectious diseases.
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