Antibody responses to an immunodominant nonstructural 1 synthetic peptide in patients with dengue fever and dengue hemorrhagic fever

Abstract

Two flaviviruses, dengue (DEN) virus and Japanese encephalitis (JE) virus, are important because of their global distribution and the frequency of epidemics in tropical and subtropical areas. To study the B-cell epitopes of nonstructural 1 (NS1) glycoprotein and anti-NS1 antibody response in DEN infection, a series of 15-mer synthetic peptides from the predicted B-cell linear epitopes of DEN-2 NS1 protein were prepared. Enzyme-linked immunosorbent assay (ELISA) was performed to analyze antibody responses to these peptides from sera of both DEN and JE patients. One peptide derived from DEN-2 NS1, D2 NS1-P1 (amino acids 1-15), was identified as the immunodominant epitope that reacted with sera from dengue fever (DF) patients but not JE patients. The isotype of D2 NS1-P1-specific antibodies was mainly immunoglobulin M (IgM) in all sera that tested positive. A specificity study demonstrated that sera from all four DEN types reacted with D2 NS1-P1. A dynamics study showed that specific antibodies to this peptide could be detected as early as 2 days after the onset of symptoms. We observed significant anti-D2 NS1-P1 antibody responses in 45% of patients with primary and secondary infections with DF or with dengue hemorrhagic fever. This is the first report demonstrating that significant anti-DEN NS1 antibodies can be induced in the sera of patients with primary DEN infection.

Antibody Responses Are Generated to Immunodominant ELK/KLE-Type Motifs on the Nonstructural-1 Glycoprotein during Live Dengue Virus Infections in Mice and Humans: Implications for Diagnosis, Pathogenesis, and Vaccine Design

“…The reaction of the human and mouse PAbs with the three peptides (amino acids 1 to 9, 3 to 11 and 5 to 13) at the amino terminus of the D-2V NS1 protein was consistent with the report that the amino acid sequence 1 DSGCVVSWKNKEL KC 15 is immunodominant in humans (17). In this study, stronger human and mouse antibody reactions were, however, observed against the three overlapping peptides (peptides 53, 54, and 55) which contained the immunodominant ELR (ELKtype motif).…”

Recombinant Multiepitope Protein for Early Detection of Dengue Infections

“…A thorough examination of the available literature revealed a single report by Huang et al (11) that described an IgM-specific dengue epitope that appeared potentially useful for the purpose of creating an IgMspecific dengue multiepitope protein. These investigators examined potential B-cell epitope-containing peptides of DEN-2 NS1 for their reactivity to IgM and IgG classes of antibodies in dengue and Japanese encephalitis (JE) patient sera.…”

“…They identified a single peptide, D2 NS1-P1, which reacted with the IgM class of antibodies in sera of dengue, but not JE, patients. This peptide, corresponding to amino acid (aa) residues 1 to 15 of DEN-2 NS1, defined a linear, immunodominant IgM-specific epitope which was reactive towards patient sera from all four dengue serotypes (11). We used this epitope as the basis for designing the recombinant dengue multiepitope protein, r-DME-M, with built-in specificity for the IgM class of antidengue antibodies.…”

Anti-Platelet and Anti-Endothelial Cell Autoantibodies in Vietnamese Infants and Children with Dengue Hemorrhagic Fever

“…A recent report showed that the isotype of NS1-P1 (aminoacids 1-15)-specific antibodies was mainly IgM in all dengue patient sera that tested positive [19] . Therefore, it is speculated that the dengue virus antigens, for example, NS1 aminoacids 1-15 which possess B-cell epitope may induce IgM autoantibodies cross-reactive with platelets.…”