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A potent neutralizing antibody with therapeutic potential against all four serotypes of dengue virus.


ABSTRACT: A therapy for dengue is still elusive. We describe the neutralizing and protective capacity of a dengue serotype-cross-reactive antibody isolated from the plasmablasts of a patient. Antibody SIgN-3C neutralized all four dengue virus serotypes at nano to picomolar concentrations and significantly decreased viremia of all serotypes in adult mice when given 2 days after infection. Moreover, mice were protected from pathology and death from a lethal dengue virus-2 infection. To avoid potential Fc-mediated uptake of immune complexes and ensuing enhanced infection, we introduced a LALA mutation in the Fc part. SIgN-3C-LALA was as efficient as the non-modified antibody in neutralizing dengue virus and in protecting mice while antibody-dependent enhancement was completely abrogated. The epitope of the antibody includes conserved amino acids in all three domains of the glycoprotein, which can explain its cross-reactivity. SIgN-3C-LALA neutralizes dengue virus both pre and post-attachment to host cells. These attributes likely contribute to the remarkable protective capacity of SIgN-3C.

SUBMITTER: Xu M 

PROVIDER: S-EPMC5627287 | biostudies-literature | 2017

REPOSITORIES: biostudies-literature

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A potent neutralizing antibody with therapeutic potential against all four serotypes of dengue virus.

Xu Meihui M   Zuest Roland R   Velumani Sumathy S   Tukijan Farhana F   Toh Ying Xiu YX   Appanna Ramapraba R   Tan Ern Yu EY   Cerny Daniela D   MacAry Paul P   Wang Cheng-I CI   Fink Katja K  

NPJ vaccines 20170123


A therapy for dengue is still elusive. We describe the neutralizing and protective capacity of a dengue serotype-cross-reactive antibody isolated from the plasmablasts of a patient. Antibody SIgN-3C neutralized all four dengue virus serotypes at nano to picomolar concentrations and significantly decreased viremia of all serotypes in adult mice when given 2 days after infection. Moreover, mice were protected from pathology and death from a lethal dengue virus-2 infection. To avoid potential Fc-me  ...[more]

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