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01.12.2018 | Research article | Ausgabe 1/2018 Open Access

BMC Infectious Diseases 1/2018

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

Zeitschrift:
BMC Infectious Diseases > Ausgabe 1/2018
Autoren:
Minh Huong Phu Ly, Meng Ling Moi, Thi Bich Hau Vu, Mya Myat Ngwe Tun, Todd Saunders, Cam Nhat Nguyen, Anh Kieu Thi Nguyen, Hung Manh Nguyen, Than Huu Dao, Do Quyen Pham, Thi Thu Thuy Nguyen, Thi Quynh Mai Le, Futoshi Hasebe, Kouichi Morita
Wichtige Hinweise

Electronic supplementary material

The online version of this article (https://​doi.​org/​10.​1186/​s12879-017-2894-7) contains supplementary material, which is available to authorized users.

Abstract

Background

Antibodies 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.

Methods

A 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.

Results

Out 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.

Conclusion

Before 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.
Zusatzmaterial
Additional file 1: Figure S1. Neutralizing antibody (N.A) profile in 34 pair serum samples obtained from 34 individuals who were DENV IgG positive pre-dengue season and demonstrated elevated DENV IgG after the season versus patient group. Neutralizing activity was determined by PRNT50 on BHK cells (A) and on FcγR-expressing BHK cells (B); Positive PRNT samples were defined as having a N.A ≥ 10 or Log2(PRNT50) ≥3.32 to any of the virus test (above dotted line). Non patient 1=pre-dengue season group; Non patient 2 = post-dengue season group; Patient = patient group. The results were represented as means of Log2 (N.A titers) ± SD. (PDF 314 kb)
12879_2017_2894_MOESM1_ESM.pdf
Additional file 2: Figure S2. Neutralizing antibody (N.A) profile in serum samples obtained from 18 individuals who were DENV IgG negative pre-dengue season but seropositive post-dengue season (Non patient) versus patient group. Neutralizing activity was determined by PRNT50 on BHK (A) and on FcγR-expressing BHK (B). Positive PRNT samples were defined as having a N.A ≥ 10 or Log2 (PRNT50) ≥3.32 to any of the virus test (above dotted line). The results were represented as means of Log2 (N.A titers) ± SD. (DOCX 55 kb)
12879_2017_2894_MOESM2_ESM.docx
Additional file 3: Figure S3. Fold-enhancement activity in serum samples obtained from 18 individuals who were DENV IgG negative pre-dengue season but seropositive post-dengue season (Non patient group) versus patient group. Fold- enhancement value was determined by the ratio of (mean plaque count at 1:20 serum dilution)/(mean plaque count in the absence of human serum samples) by using FcγR expressing BHK cells. Positive infection-enhancing activity was defined as fold-enhancement value greater than cut-off value plus 2 times SD (above dash line). P-value was determined by Mann -Whitney test. P value £0.05 = significant. Non patient = Non patient group; Patient = Patient group. NA(-): Neutralizing antibody titer <10; NA(+): Neutralizing antibody titer ≥ 10. The results were represented as Median ±IQR. (DOCX 21 kb)
12879_2017_2894_MOESM3_ESM.docx
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