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.

Jisang Park,Le Quynh Mai,Ly Tuan Khai,Yong-Suk Jang,Nguyen Thi Thu Thuy,Hyun-Young Lee

doi:10.3390/vaccines8010088

Jisang Park, Le Quynh Mai + Show 4 more

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https://doi.org/10.3390/vaccines8010088

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Abstract

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.

Highlights

Dengue virus (DENV) is an arthropod-borne single positive-strand RNA virus and a causative agent of several diseases [1,2]
Anti-envelope domain II (EDII)-consensus envelope domain III (cEDIII) Ab protected against DENV1, 2, and 4 challenge
The reduction in the level of DENV1-infected monocytes was significantly (DCs), we evaluated the levels of DENV infection in blood cells

Summary

Introduction

Dengue virus (DENV) is an arthropod-borne single positive-strand RNA virus and a causative agent of several diseases [1,2]. There are four antigenically-related serotypes of DENV. Since the 1950s, geographical expansion of DENV-infected diseases has occurred due to the global warming-induced increase in the area suitable as habitat for its host mosquitoes (Aedes aegypti and Aedes albopictus). 390 million people are estimated to be infected with DENV annually, 96 million of whom show clinical symptoms [1,2,3]. DENV causes a spectrum of conditions from self-limited mild dengue fever to severe dengue hemorrhagic fever and dengue shock syndrome [1,2].

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