Dengue virus infection-enhancement activity in neutralizing antibodies of healthy adults before dengue season as determined by using FcγR-expressing cells

Abstract

BackgroundAntibodies are critical responses to protect the host from dengue virus(DENV) infection. Antibodies target DENV by two pathologic mechanisms: virus neutralization and infection enhancement. In dengue patients, the absence of neutralizing activity in the presence of FcγR implies that infection-enhancing activity hampers the neutralizing activity of antibodies, which could potentially lead to symptomatic presentations and severe clinical outcomes.MethodsA total of 100 pair serum samples from adult healthy volunteers were obtained during the dengue season in Ha Noi in 2015 for evaluation of neutralizing and infection-enhancing activity. Additionally, 20 serum samples from acute secondary DENV infection patients were also used as the patient group in this study. PRNT was performed on BHK cells and FcγR-expressing BHK cell lines for all serum samples.ResultsOut of 100 residents, positive neutralizing antibodies (N.A) were found in 44.23 and 76.92% for DENV-1; 38.46 and 75% for DENV-2; 19.23 and 15.38% for DENV-3; and 1.92 and 9.62% for DENV-4 for pre and post-dengue season respectively. The percentage of post-exposure residents having positive responses against single, two, or more than three DENV serotypes were 38.46, 44.23 and 15.38%, respectively. A total of 34 residents were DENV seropositive before the dengue season and these individuals demonstrated further elevation of IgG antibodies after the dengue season. At the end of the season, 18 residents were confirmed to be new asymptomatic DENV infection cases. In both groups, N.A titers determined on BHK cells were higher than that on FcγR-expressing BHK cells. In heterotypic N.A responses, N.A titers to the infecting serotype from the samples obtained from pre-exposure group were significantly higher than those of the patient group. However, fold enhancement to the infecting serotypes from the samples in the pre-exposure group was substantially lower as compared to that of the patient group.ConclusionBefore and after the dengue season, serum samples from healthy volunteers demonstrated high levels of neutralizing antibodies and low or absence of infection-enhancement activity. The results suggest that while infection-enhancement activity hampers neutralizing activity of antibodies, high levels of DENV neutralizing antibodies set a critical threshold in facilitating the prevention of disease progression.Electronic supplementary materialThe online version of this article (10.1186/s12879-017-2894-7) contains supplementary material, which is available to authorized users.

A Simple and High-Throughput ELISA-Based Neutralization Assay for the Determination of Anti-Flavivirus Neutralizing Antibodies

“…The results on the DENV IgG+ clinical samples demonstrated that the DENV-EMNT performed on conventional BHK-21 cells (non-FcγR cells) showed higher neutralizing titers as compared to the FcγRIIA-expressing BHK-21 cells. These results are consistent with previous studies in which DENV neutralizing titers were higher in FcγR-negative cells [11,[49][50][51].…”

Flavivirus Receptors: Diversity, Identity, and Cell Entry

“…ADE has been linked to the observation that one flavivirus infection can enhance another ( 84 ). However, a recent study showed that ADE is dependent on the level of neutralizing antibodies, particularly IgG and IgM ( 85 ); only patients with a low level of neutralizing antibodies showed enhancement of DENV infection ( 85 ). Antibodies, even at low concentration, against the EDIII domain were able to block viral entry of the four DENV serotypes without inducing antibody-dependent enhancement ( 86 ).…”

Urban transmission of mosquito-borne flaviviruses – a review of the risk for humans in Vietnam

“…Dengue was first reported in Vietnam in 1959 [55] and dengue has since then become endemic across the country with the circulation of all four serotypes [41,[56][57][58][59][60]. Nevertheless, there is a spatial heterogeneity in DENV transmission in Vietnam and the incidence rate differs for each region and province.…”

“…The latest as well as the largest DF outbreak so far in Hanoi occurred in 2017 with 37,651 cases and 7 deaths [66]. Four DENV serotypes (1-4) have been confirmed to co-exist in Hanoi [59]. Previous studies also revealed that the DF cases were mainly concentrated to the central urban districts [65,[67][68][69]].…”