How NS1 Antibodies Prevent Severe Flavivirus Disease

doi:10.1016/j.tibs.2021.03.005

Trends in Biochemical Sciences

Volume 46, Issue 7, July 2021, Pages 519-521

https://doi.org/10.1016/j.tibs.2021.03.005 Get rights and content

The flavivirus genus consists of several major human pathogens including dengue (DENV) and Zika viruses. The flavivirus nonstructural protein 1 (NS1) plays an important role in disease progression, for example, in the development of severe dengue disease. Anti-NS1 antibodies have been shown to confer protection, and two new studies by Biering et al. and Modhiran et al. on the structure of NS1:antibody complexes reveal their mechanism of neutralization.

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Declaration of Interests

The authors declare no conflicts of interest.

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Dengue virus NS1 triggers endothelial permeability and vascular leak that is prevented by NS1 vaccination
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Structure-guided insights on the role of NS1 in flavivirus infection
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Flavivirus NS1 triggers tissue-specific vascular endothelial dysfunction reflecting disease tropism
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There are more references available in the full text version of this article.

Cited by (5)

NS1: a promising novel target antigen with strong immunogenicity and protective efficacy for avian flavivirus vaccine development
2024, Poultry Science
Tembusu virus (TMUV), an avian pathogenic flavivirus, has emerged as a significant threat to the duck industry in Southeast Asia, causing substantial economic losses. Due to the antibody-dependent enhancement (ADE) effect of TMUV subneutralizing antibodies, there is a pressing need to further develop new TMUV vaccine target antigens that ensure both safety and efficacy. Here, the TMUV non-structural protein 1 (NS1) as a target for development of effective anti-TMUV vaccines was unveiled. The amino acid sequences of TMUV NS1 exhibit a high degree of conservation across different strains (92.63–100%). To investigate the potential of TMUV NS1 as a vaccine target, the TMUV NS1-based plasmids were constructed and identified the C-terminal 30 amino acids residues of TMUV E (E_C30) as an effective signal peptide for promoting NS1 expression and secretion. Subsequently, the plasmid pVAX1-E_C30-NS1 was employed to immunize ducks, resulting in specific anti-NS1 IgG responses being stimulated, while without inducing anti-TMUV neutralizing antibodies. Furthermore, the cellular immune responses triggered by the TMUV NS1 were evaluated, observing a notable increase in lymphocyte proliferation at 4 wk and 6 wk postinjection with the pVAX1-E_C30-NS1. Additionally, there was a significant up-regulation of NS1-specific Il-4 and Ifnγ levels at these time points. Following this, ducks from different groups were challenged with TMUV, and remarkably, those immunized with the NS1 vaccine displayed significantly lower viral copies both at 3 d postinfection (dpi) and 7 dpi (P < 0.05) compared to ducks immunized with the control vector. Notably, the NS1 demonstrated remarkable protection against TMUV challenge without causing severe gross lesions. Collectively, these findings highlighted the impressive immunogenicity and protectivity of the TMUV NS1. Consequently, NS1 holds great promise as a novel antigen target for the development of efficient and safe TMUV vaccines.
Linear epitope identification of monoclonal antibodies against the duck Tembusu virus NS1
2023, Poultry Science
Since 2010, the duck Tembusu virus (DTMUV) has caused a severe outbreak of egg drop syndrome in laying ducks in China, which has resulted in substantial financial losses in the poultry industry. DTMUV nonstructural protein 1 (NS1), as the only secreted protein, could aid in the development of therapeutic antibodies and diagnostic techniques; however, there are few studies on the preparation and epitope identification of monoclonal antibodies (mAbs) against DTMUV NS1. In this study, by indirect enzyme-linked immunosorbent assay (ELISA), Western blotting, and indirect immunofluorescence assay, we screened 6 mAbs (8A4, 8E6, 10F12, 1H11, 3D5, 5C11) that could specifically recognize DTMUV NS1. For epitope mapping of mAbs, a series of GST-tagged truncated fusion proteins of DTMUV NS1 were constructed by prokaryotic expression. Finally, the 4 shortest linear epitopes were identified by indirect ELISA and Western blotting. The epitope ¹³³FVIDGPK¹³⁹ was recognized by 8A4, the epitope ²⁴³IPKTLGGP²⁵⁰ was recognized by 8E6, the epitope ²⁶⁷PWDEK²⁷¹ was recognized by 10F12, and ¹⁵⁶EDFGFGVL¹⁶³ was recognized by 1H11, 3D5, and 5C11. By sequence alignment and cross-reaction tests, we found that 8A4 and 8E6 had high specificity for DTMUV NS1 compared with that of other mAbs, but 10F12, 1H11, 3D5, and 5C11 exhibited a clear degree of cross-reaction with dengue virus (DENV), Japanese encephalitis virus (JEV), West Nile virus (WNV), and Zika virus (ZIKV) NS1. Finally, the predicted crystal structure analysis showed the approximate spatial positions of the 4 epitopes on the NS1 dimer. In summary, our study revealed 2 specific mAbs for DTMUV NS1 recognition and 4 multiflavivirus mAbs for DENV, JEV, WNV, and ZIKV NS1 recognition.
A Perspective on Current Flavivirus Vaccine Development: A Brief Review
2023, Viruses
Trends and validation in impedimetric immunosensors in the application of routine analysis
2022, Advances in Bioelectrochemistry
Fundamentals for Virus and Antigen Detection in Immunotechnologies
2022, Advances in Bioelectrochemistry Volume 3: Biosensors, Wearable Devices and Biomedical Applications

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Trends in Biochemical Sciences

SpotlightHow NS1 Antibodies Prevent Severe Flavivirus Disease

Section snippets

Declaration of Interests

The good, the bad, and the shocking: the multiple roles of dengue virus nonstructural protein 1 in protection and pathogenesis

Annu. Rev. Virol.

Dengue virus NS1 triggers endothelial permeability and vascular leak that is prevented by NS1 vaccination

Sci. Transl. Med.

Structure-guided insights on the role of NS1 in flavivirus infection

Bioessays

Flavivirus NS1 triggers tissue-specific vascular endothelial dysfunction reflecting disease tropism

Cell Rep.

Spotlight
How NS1 Antibodies Prevent Severe Flavivirus Disease