Immunogenicity of dengue virus type 1 DNA vaccines expressing truncated and full length envelope protein

ABSTRACT Dengue virus relies on a conformational change in its envelope protein, E, to fuse the viral lipid membrane with the endosomal membrane and thereby deliver the viral genome into the cytosol. We have determined the crystal structure of a soluble fragment E (sE) of dengue virus type 1 (DEN-1). The protein is in the postfusion conformation even though it was not exposed to a lipid membrane or detergent. At the domain I-domain III interface, 4 polar residues form a tight cluster that is absent in other flaviviral postfusion structures. Two of these residues, His-282 and His-317, are conserved in flaviviruses and are part of the “pH sensor” that triggers the fusogenic conformational change in E, at the reduced pH of the endosome. In the fusion loop, Phe-108 adopts a distinct conformation, forming additional trimer contacts and filling the bowl-shaped concavity observed at the tip of the DEN-2 sE trimer.

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DNA Vaccines against Dengue Virus Type 2 Based on Truncate Envelope Protein or Its Domain III

PLoS ONE ◽

10.1371/journal.pone.0020528 ◽

2011 ◽

Vol 6 (7) ◽

pp. e20528 ◽

Cited By ~ 27

Author(s):

Adriana S. Azevedo ◽

Anna M. Y. Yamamura ◽

Marcos S. Freire ◽

Gisela F. Trindade ◽

Myrna Bonaldo ◽

...

Keyword(s):

Dengue Virus ◽

Virus Type ◽

Envelope Protein ◽

Dna Vaccines ◽

Domain Iii ◽

Dengue Virus Type 2

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A potent neutralizing mouse monoclonal antibody specific to dengue virus type 1 Mochizuki strain recognized a novel epitope around the N-67 glycan on the envelope protein: a possible explanation of dengue virus evolution regarding the acquisition of N-67 glycan

Virus Research ◽

10.1016/j.virusres.2020.198278 ◽

2020 ◽

pp. 198278

Author(s):

Tomohiro Kotaki ◽

Atsushi Yamanaka ◽

Eiji Konishi ◽

Masanori Kameoka

Keyword(s):

Monoclonal Antibody ◽

Dengue Virus ◽

Virus Type ◽

Envelope Protein ◽

Protein A ◽

Virus Evolution ◽

Mouse Monoclonal Antibody

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Comparison of infection-neutralizing and -enhancing antibody balance induced by two distinct genotype strains of dengue virus type 1 or 3 DNA vaccines in mice

Microbes and Infection ◽

10.1016/j.micinf.2013.07.008 ◽

2013 ◽

Vol 15 (12) ◽

pp. 828-836 ◽

Cited By ~ 5

Author(s):

Fithriyah Sjatha ◽

Yamato Takizawa ◽

Tomohiro Kotaki ◽

Atsushi Yamanaka ◽

Eiji Konishi

Keyword(s):

Dengue Virus ◽

Virus Type ◽

Dna Vaccines ◽

Distinct Genotype

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A Mouse Monoclonal Antibody against Dengue Virus Type 1 Mochizuki Strain Targeting Envelope Protein Domain II and Displaying Strongly Neutralizing but Not Enhancing Activity

Journal of Virology ◽

10.1128/jvi.01874-13 ◽

2013 ◽

Vol 87 (23) ◽

pp. 12828-12837 ◽

Cited By ~ 15

Author(s):

Atsushi Yamanaka ◽

Tomohiro Kotaki ◽

Eiji Konishi

Keyword(s):

Dengue Virus ◽

Virus Type ◽

Envelope Protein ◽

Hemorrhagic Fever ◽

Severe Form ◽

Antibody Engineering ◽

Protein Domain ◽

Enzyme Linked Immunosorbent Assay ◽

Neutralizing Activity

Dengue fever and its more severe form, dengue hemorrhagic fever, are major global concerns. Infection-enhancing antibodies are major factors hypothetically contributing to increased disease severity. In this study, we generated 26 monoclonal antibodies (MAbs) against the dengue virus type 1 Mochizuki strain. We selected this strain because a relatively large number of unique and rare amino acids were found on its envelope protein. Although most MAbs showing neutralizing activities exhibited enhancing activities at subneutralizing doses, one MAb (D1-IV-7F4 [7F4]) displayed neutralizing activities without showing enhancing activities at lower concentrations. In contrast, another MAb (D1-V-3H12 [3H12]) exhibited only enhancing activities, which were suppressed by pretreatment of cells with anti-FcγRIIa. Although antibody engineering revealed that antibody subclass significantly affected 7F4 (IgG3) and 3H12 (IgG1) activities, neutralizing/enhancing activities were also dependent on the epitope targeted by the antibody. 7F4 recognized an epitope on the envelope protein containing E118 (domain II) and had a neutralizing activity 10- to 1,000-fold stronger than the neutralizing activity of previously reported human or humanized neutralizing MAbs targeting domain I and/or domain II. An epitope-blocking enzyme-linked immunosorbent assay (ELISA) indicated that a dengue virus-immune population possessed antibodies sharing an epitope with 7F4. Our results demonstrating induction of these antibody species (7F4 and 3H12) in Mochizuki-immunized mice may have implications for dengue vaccine strategies designed to minimize induction of enhancing antibodies in vaccinated humans.

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