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

Autor:	Xu M; Singapore Immunology Network, Agency for Science, Technology and Research, Singapore, Singapore., Zuest R; Singapore Immunology Network, Agency for Science, Technology and Research, Singapore, Singapore., Velumani S; Singapore Immunology Network, Agency for Science, Technology and Research, Singapore, Singapore., Tukijan F; Singapore Immunology Network, Agency for Science, Technology and Research, Singapore, Singapore., Toh YX; Singapore Immunology Network, Agency for Science, Technology and Research, Singapore, Singapore., Appanna R; Singapore Immunology Network, Agency for Science, Technology and Research, Singapore, Singapore., Tan EY; Department of General Surgery, Tan Tock Seng Hospital, Singapore, Singapore., Cerny D; Singapore Immunology Network, Agency for Science, Technology and Research, Singapore, Singapore.; School of Biological Sciences, Nanyang Technological University, Singapore, Singapore., MacAry P; Yong Loo Lin School of Medicine, National University of Singapore, Singapore, Singapore., Wang CI; Singapore Immunology Network, Agency for Science, Technology and Research, Singapore, Singapore., Fink K; Singapore Immunology Network, Agency for Science, Technology and Research, Singapore, Singapore.; School of Biological Sciences, Nanyang Technological University, Singapore, Singapore.
Jazyk:	angličtina
Zdroj:	NPJ vaccines [NPJ Vaccines] 2017 Jan 23; Vol. 2, pp. 2. Date of Electronic Publication: 2017 Jan 23 (Print Publication: 2017).
DOI:	10.1038/s41541-016-0003-3
Abstrakt:	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.
Databáze:	MEDLINE
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