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Open AccessArticle

Addition of Partial Envelope Domain II into Envelope Domain III of Dengue Virus Antigen Potentiates the Induction of Virus-Neutralizing Antibodies and Induces Protective Immunity

1
Department of Bioactive Material Sciences and Research Center of Bioactive Materials, Jeonbuk National University, Jeonju 54896, Korea
2
Department of Hematology, 108 Military Central Hospital, Hanoi 113601, Vietnam
3
National Institute of Hygiene and Epidemiology, Hanoi 100000, Vietnam
4
Department of Molecular Biology and The Institute for Molecular Biology and Genetics, Jeonbuk National University, Jeonju 54896, Korea
*
Author to whom correspondence should be addressed.
Present address: ProteomeTech Inc., Seoul 07528, Korea.
Vaccines 2020, 8(1), 88; https://doi.org/10.3390/vaccines8010088
Received: 17 January 2020 / Revised: 5 February 2020 / Accepted: 10 February 2020 / Published: 15 February 2020
(This article belongs to the Special Issue Current Flavivirus Research Important for Vaccine Development )
Dengue virus (DENV) comprises four serotypes in the family Flaviviridae and is a causative agent of dengue-related diseases, including dengue fever. Dengue fever is generally a self-limited febrile illness. However, secondary infection of patients with a suboptimal antibody (Ab) response provokes life-threatening severe dengue hemorrhagic fever or dengue shock syndrome. To develop a potent candidate subunit vaccine against DENV infection, we developed the EDII-cEDIII antigen, which contains partial envelope domain II (EDII) including the fusion loop and BC loop epitopes together with consensus envelope domain III (cEDIII) of all four serotypes of DENV. We purified Ab from mice after immunization with EDII-cEDIII or cEDIII and compared their virus neutralization and Ab-dependent enhancement of DENV infection. Anti-EDII-cEDIII Ab showed stronger neutralizing activity and lower Ab-dependent peak enhancement of DENV infection compared with anti-cEDIII Ab. Following injection of Ab-treated DENV into AG129 mice, anti-EDII-cEDIII Ab ameliorated DENV infection in tissues with primary and secondary infection more effectively than anti-cEDIII Ab. In addition, anti-EDII-cEDIII Ab protected against DENV1, 2, and 4 challenge. We conclude that EDII-cEDIII induces neutralizing and protective Abs, and thus, shows promise as a candidate subunit vaccine for DENV infection. View Full-Text
Keywords: dengue virus; subunit vaccine; antibody-dependent enhancement; antibody dengue virus; subunit vaccine; antibody-dependent enhancement; antibody
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Park, J.; Lee, H.-Y.; Khai, L.T.; Thuy, N.T.T.; Mai, L.Q.; Jang, Y.-S. Addition of Partial Envelope Domain II into Envelope Domain III of Dengue Virus Antigen Potentiates the Induction of Virus-Neutralizing Antibodies and Induces Protective Immunity. Vaccines 2020, 8, 88.

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