A Novel Single-Dose Dengue Subunit Vaccine Induces Memory Immune Responses

Chen-Yi Chiang,Hsin-Wei Chen,Jy-Ping Tsai,Yi-Shiuan Li,Hsueh-Hung Liu,Pele Chong,Shih-Jen Liu,Mei-Yu Chen,Chih-Hsiang Leng,Lisa Ng Fong Poh

doi:10.1371/journal.pone.0023319

Chen-Yi Chiang, Hsin-Wei Chen + Show 8 more

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https://doi.org/10.1371/journal.pone.0023319

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Abstract

To protect against dengue viral infection, a novel lipidated dengue subunit vaccine was rationally designed to contain the consensus amino acid sequences derived from four serotypes of dengue viruses. We found that the lipidated consensus dengue virus envelope protein domain III (LcED III) is capable of activating antigen-presenting cells and enhancing cellular and humoral immune responses. A single-dose of LcED III immunization in mice without extra adjuvant formulation is sufficient to elicit neutralizing antibodies against all four serotypes of dengue viruses. In addition, strong memory responses were elicited in mice immunized with a single-dose of LcED III. Quick, anamnestic neutralizing antibody responses to a live dengue virus challenge were elicited at week 28 post-immunization. These results demonstrate the promising possibility of a future successful tetravalent vaccine against dengue viral infections that utilizes one-dose vaccination with LcED III.

Highlights

The dengue viruses (DV) are members of the Flavivirus genus of the Flaviviridae family
It has been demonstrated that envelope protein domain III is a leading target in dengue subunit vaccine development [46]
Without the addition of proper adjuvant, consensus dengue virus envelope protein domain III (cED III) alone induced low neutralizing antibody responses. To overcome this inherent problem of subunit vaccines, we developed LcED III as a novel dengue vaccine candidate that has a built-in intrinsic adjuvant

Summary

Introduction

The dengue viruses (DV) are members of the Flavivirus genus of the Flaviviridae family. There are four antigenically different serotypes (DV-1 through DV-4) of DV [1]. Each of the four serotypes of dengue viral infection is able to cause dengue fever, which is generally a self-limited febrile illness. Certain dengue-infected individuals develop the life-threatening dengue hemorrhagic fever (DHF) or dengue shock syndrome (DSS) [2,3]. The pathogeneses of DHF and DSS are complicated and still not fully understood.

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