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Identification of a Zika NS2B Epitope for Which Absence of IgG Response Is Associated with Severe Neurological Symptoms and the Design of a Biomarker Capable of Discriminatory Diagnostics Between Severe and Non4 Severe Clinical Phenotypes

08 March 2021, Version 1

Abstract

In this manuscript we describe the engineering of a biomarker for the diagnosis and prognosis of Zika-associated neurological disease. Although the causal association between congenital Zika virus (ZIKV) infection and neurological manifestations has been well documented in the recent years, biomarkers for proper diagnostic and disease outcome still remain to be defined. Combining high-density peptide array and multivariate analysis, we have identified an ZIKV epitope that is associated to a lack of IgG antibody response in patients with severe neurological symptoms. An engineered chimera was developed to discriminate between mild and severe clinical forms of the disease.

Keywords

flavivirus
Dengue
Diagnosis
Antibody response
Peptide array
Neurological manifestations

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Version History

Mar 08, 2021 Version 1

Version Notes

Original version. File contains full manuscript and supplemental information.

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The content is available under CC BY NC ND 4.0 [opens in a new tab]

DOI

10.26434/chemrxiv.14170439.v1
D O I: 10.26434/chemrxiv.14170439.v1 [opens in a new tab]

Funding

This study was supported by grants from the German Research Foundation (DFG) via the Heidelberg Karlsruhe Research Partnership (HEiKA to TJ and FFL), the European Commission (IDAMS FP7 281803, ZIKAlliance H2020 734548), the German Centre for Infection Research (DZIF), Heidelberg Site, CuraZika Foundation, FACEPE, NUQAAPE, CAPES, CNPq, INCT-FCx, FAPESP (2019/01255-9) and the German Federal Ministry of Education and Research (NanoMatFutur grant 13XP5050A). Computer allocation was partly granted by the Brazilian National Scientific Computing Center (LNCC). The company PEPperPRINT based in Heidelberg supported the design and printing of the peptide microarrays. The funders had no role in study design, data collection and analysis, decision to publish, or preparation of the manuscript.

Author’s competing interest statement

A patent application for the epitope has been filed by TJ, NF, FFL, TM, and ETA. A patent application for the engineered protein carrying the identified NS2B epitope has been filed by RDL, DFC and IFTV. Otherwise, the authors have declared that they have no competing interests.

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