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

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 t...

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Main Authors: 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
Format: Article
Language:English
Published: BMC 2018-01-01
Series:BMC Infectious Diseases
Subjects:
Online Access:http://link.springer.com/article/10.1186/s12879-017-2894-7
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author 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
author_facet 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
author_sort Minh Huong Phu Ly
collection DOAJ
description 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.
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spelling doaj.art-199e179cce1b439888d5c75a6b9080812022-12-22T00:01:09ZengBMCBMC Infectious Diseases1471-23342018-01-0118111210.1186/s12879-017-2894-7Dengue virus infection-enhancement activity in neutralizing antibodies of healthy adults before dengue season as determined by using FcγR-expressing cellsMinh Huong Phu Ly0Meng Ling Moi1Thi Bich Hau Vu2Mya Myat Ngwe Tun3Todd Saunders4Cam Nhat Nguyen5Anh Kieu Thi Nguyen6Hung Manh Nguyen7Than Huu Dao8Do Quyen Pham9Thi Thu Thuy Nguyen10Thi Quynh Mai Le11Futoshi Hasebe12Kouichi Morita13Department of Virology, Institute of Tropical Medicine, Nagasaki UniversityDepartment of Virology, Institute of Tropical Medicine, Nagasaki UniversityDepartment of Virology, National Institute of Hygiene and EpidemiologyDepartment of Virology, Institute of Tropical Medicine, Nagasaki UniversityGraduate School of Biomedical Sciences, Nagasaki UniversityHa Noi Preventive Medicine CenterHa Noi Preventive Medicine CenterHa Noi Preventive Medicine CenterHa Noi Preventive Medicine CenterDepartment of Virology, National Institute of Hygiene and EpidemiologyDepartment of Virology, National Institute of Hygiene and EpidemiologyDepartment of Virology, National Institute of Hygiene and EpidemiologyVietnam Research Station, Center for Infectious Disease Research in Asia and Africa, Institute of Tropical Medicine, Nagasaki UniversityDepartment of Virology, Institute of Tropical Medicine, Nagasaki UniversityAbstract 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.http://link.springer.com/article/10.1186/s12879-017-2894-7Dengue virus (DENV)Dengue virus neutralizing antibodyPrimary DENV infectionSecondary DENV infectionMonotypic, heterotypic immune response
spellingShingle 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
Dengue virus infection-enhancement activity in neutralizing antibodies of healthy adults before dengue season as determined by using FcγR-expressing cells
BMC Infectious Diseases
Dengue virus (DENV)
Dengue virus neutralizing antibody
Primary DENV infection
Secondary DENV infection
Monotypic, heterotypic immune response
title Dengue virus infection-enhancement activity in neutralizing antibodies of healthy adults before dengue season as determined by using FcγR-expressing cells
title_full Dengue virus infection-enhancement activity in neutralizing antibodies of healthy adults before dengue season as determined by using FcγR-expressing cells
title_fullStr Dengue virus infection-enhancement activity in neutralizing antibodies of healthy adults before dengue season as determined by using FcγR-expressing cells
title_full_unstemmed Dengue virus infection-enhancement activity in neutralizing antibodies of healthy adults before dengue season as determined by using FcγR-expressing cells
title_short Dengue virus infection-enhancement activity in neutralizing antibodies of healthy adults before dengue season as determined by using FcγR-expressing cells
title_sort dengue virus infection enhancement activity in neutralizing antibodies of healthy adults before dengue season as determined by using fcγr expressing cells
topic Dengue virus (DENV)
Dengue virus neutralizing antibody
Primary DENV infection
Secondary DENV infection
Monotypic, heterotypic immune response
url http://link.springer.com/article/10.1186/s12879-017-2894-7
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