Potential Protective Effect of Dengue NS1 Human Monoclonal Antibodies against Dengue and Zika Virus Infections.

Content Provider	Europe PMC
Author	Sootichote, Rochanawan Puangmanee, Wilarat Benjathummarak, Surachet Kowaboot, Siriporn Yamanaka, Atsushi Boonnak, Korbporn Ampawong, Sumate Chatchen, Supawat Ramasoota, Pongrama Pitaksajjakul, Pannamthip
Editor	Wakao, Hiroshi
Copyright Year	2023
Abstract	Due to the lack of an effective therapeutic treatment to flavivirus, dengue virus (DENV) nonstructural protein 1 (NS1) has been considered to develop a vaccine owing to its lack of a role in antibody-dependent enhancement (ADE). However, both NS1 and its antibody have shown cross-reactivity to host molecules and have stimulated anti-DENV NS1 antibody-mediated endothelial damage and platelet dysfunction. To overcome the pathogenic events and reactogenicity, human monoclonal antibodies (HuMAbs) against DENV NS1 were generated from DENV-infected patients. Herein, the four DENV NS1-specific HuMAbs revealed the therapeutic effects in viral neutralization, reduction of viral replication, and enhancement of cell cytolysis of DENV and zika virus (ZIKV) via complement pathway. Furthermore, we demonstrate that DENV and ZIKV NS1 trigger endothelial dysfunction, leading to vascular permeability in vitro. Nevertheless, the pathogenic effects from NS1 were impeded by 2 HuMAbs (D25-4D4C3 and D25-2B11E7) and also protected the massive cytokines stimulation (interleukin [IL-]-1b, IL-1ra, IL-2, IL-4, IL-5, IL-6, IL-8, IL-9, IL-13, IL-17, eotaxin, granulocyte colony-stimulating factor, granulocyte-macrophage colony-stimulating factor, Inducible protein-10, monocyte chemoattractant protein-1, macrophage inflammatory protein [MIP]-1 α, MIP-1β, tumor necrosis factor-α, platelet-derived growth factor, and RANTES). Collectively, our findings suggest that the novel protective NS1 monoclonal antibodies generated from humans has multiple therapeutic benefits against DENV and ZIKV infections.
Journal	Biomedicines
Volume Number	11
PubMed Central reference number	PMC9855337
Issue Number	1
PubMed reference number	36672734
e-ISSN	22279059
DOI	10.3390/biomedicines11010227
Language	English
Publisher	MDPI
Publisher Date	2023-01-16
Access Restriction	Open
Rights License	Licensee MDPI, Basel, Switzerland. This article is an open access article distributed under the terms and conditions of the Creative Commons Attribution (CC BY) license (https://creativecommons.org/licenses/by/4.0/). © 2023 by the authors.
Subject Keyword	dengue virus Zika virus dengue non-structural protein 1 human monoclonal antibody neutralization vascular leakage therapeutic antibody
Content Type	Text
Resource Type	Article
Subject	Medicine Biochemistry, Genetics and Molecular Biology