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- Title
A potent neutralizing antibody with therapeutic potential against all four serotypes of dengue virus.
- Authors
Xu, Meihui; Zuest, Roland; Velumani, Sumathy; Tukijan, Farhana; Toh, Ying Xiu; Appanna, Ramapraba; Tan, Ern Yu; Cerny, Daniela; MacAry, Paul; Wang, Cheng-I; Fink, Katja
- 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. Dengue: A single vaccine candidate for all strains An antibody-vaccine candidate has been discovered that neutralizes and confers protection against all four strains of dengue virus. Katja Fink, of the Singapore Immunology Network and Nanyang Technological University, Singapore, describes this as the first time a highly neutralizing antibody has shown efficacy against all four strains. Fink's team, consisting of scientists from institutions across the country, tested the candidate (SIgN-3C-LALA) in both pre-exposure and post-exposure mouse models. The findings showed it reduced blood-virus levels, protected from lethal infection, and also offered improved safety—without compromising efficacy—the latter by way of intentional mutations to the antibody's structure. As the global cost of dengue treatment is as high as 9 billion US$ per year, further study is needed to evaluate the suitability of the antibody candidate for the treatment of dengue in humans.
- Subjects
IMMUNOGLOBULINS; DENGUE viruses; SEROTYPES; VIREMIA; IMMUNE complexes
- Publication
NPJ Vaccines, 2017, Vol 2, Issue 1, pN.PAG
- ISSN
2059-0105
- Publication type
Article
- DOI
10.1038/s41541-016-0003-3