Open AccessA potent neutralizing antibody with therapeutic potential against all four serotypes of dengue virus
Author(s) -
Meihui Xu,
Roland Zuest,
Sumathy Velumani,
Farhana Tukijan,
Ying Xiu Toh,
Ramapraba Appanna,
Ern Yu Tan,
Daniela Cerny,
Paul A. MacAry,
ChengI Wang,
Katja Fink
Publication year - 2017
Publication title -
npj vaccines
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 2.691
H-Index - 22
ISSN - 2059-0105
DOI - 10.1038/s41541-016-0003-3
Subject(s) - dengue virus , dengue fever , virology , antibody dependent enhancement , antibody , serotype , neutralizing antibody , viremia , virus , dengue vaccine , epitope , biology , immune system , immunology
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.