- Recombinant Protein Mimicking the Antigenic Structure of the Viral Surface Envelope Protein Reinforces Induction of an Antigen‑Specific and Virus‑Neutralizing Immune Response Against Dengue Virus
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Ju Kim , Tae Young Lim , Jisang Park , Yong&#
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J. Microbiol. 2023;61(1):131-143. Published online February 1, 2023
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DOI: https://doi.org/10.1007/s12275-023-00021-z
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Dengue virus (DENV), belonging to the family Flaviviridae, is the causative agent of dengue and comprises four serotypes.
A second heterologous DENV infection is a critical risk factor for severe dengue, and no effective vaccine is available to
prevent infection by all four DENV serotypes. Recombinant DENV vaccines are primarily based on the envelope proteins,
prM and E. The E protein and its envelope domain III (EDIII) have been investigated as candidate antigens (Ags) for
recombinant subunit vaccines. However, most EDIII-based Ags are monomers that do not display the cognate antigenic
structure of E protein, which is essential for induction of virus-neutralizing immunity. Here, we developed recombinant
DENV-2 envelope domain (r2ED) protein as an Ag that mimics the quaternary structure of E protein on the DENV surface.
We confirmed that r2ED retained the conformational epitope displayed at the E-dimer interface, which reportedly exhibits
broad virus-neutralizing capacity, without displaying the fusion loop epitope that causes antibody (Ab)-dependent enhancement.
Furthermore, compared with EDIII alone, r2ED elicited stronger Ag-specific and cross-reactive neutralizing Ab and
T cell-mediated immune responses in mice. This Ag-specific immunity was maintained at an elevated level 6 months after
the last immunization, suggesting sustained Ag-specific immune memory. Taken together, these observations suggest that
r2ED could be used to develop an improved subunit vaccine capable of inducing a broadly cross-reactive and long-lasting
immune response against DENV infection.
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Citations
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- Current status and perspectives on vaccine development against dengue virus infection
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Jisang Park , Ju Kim , Yong-Suk Jang
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J. Microbiol. 2022;60(3):247-254. Published online February 14, 2022
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DOI: https://doi.org/10.1007/s12275-022-1625-y
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Abstract
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Dengue virus (DENV) consists of four serotypes in the family
Flaviviridae and is a causative agent of dengue fever, dengue
hemorrhagic fever, and dengue shock syndrome. DENV is
transmitted by mosquitoes, Aedes aegypti and A. albopictus,
and is mainly observed in areas where vector mosquitoes live.
The number of dengue cases reported by the World Health
Organization increased more than 8-fold over the last two
decades from 505,430 in 2000 to over 2.4 million in 2010 to
5.2 million in 2019. Although vaccine is the most effective
method
against DENV, only one commercialized vaccine exists,
and it cannot be administered to children under 9 years of
age. Currently, many researchers are working to resolve the
various problems hindering the development of effective dengue
vaccines; understanding of the viral antigen configuration
would provide insight into the development of effective
vaccines against DENV infection. In this review, the current
status and perspectives on effective vaccine development for
DENV are examined. In addition, a plausible direction for
effective vaccine development against DENV is suggested.
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