PT  - JOURNAL ARTICLE
AU  - Siti Naqiah Amrun
AU  - Wearn-Xin Yee
AU  - Farhana Abu Bakar
AU  - Bernett Lee
AU  - Yiu-Wing Kam
AU  - Fok-Moon Lum
AU  - Jeslin J.L. Tan
AU  - Vanessa W.X. Lim
AU  - Wanitda Watthanaworawit
AU  - Clare Ling
AU  - Francois Nosten
AU  - Laurent Renia
AU  - Yee-Sin Leo
AU  - Lisa F.P. Ng
TI  - Novel differential linear B-cell epitopes to identify Zika and dengue virus infections in patients
AID  - 10.1101/639542
DP  - 2019 Jan 01
TA  - bioRxiv
PG  - 639542
4099  - http://biorxiv.org/content/early/2019/05/16/639542.short
4100  - http://biorxiv.org/content/early/2019/05/16/639542.full
AB  - Background Recent Zika virus (ZIKV) outbreaks challenged existing laboratory diagnostic standards, especially for serology-based methods. Due to the genetic and structural similarity of ZIKV with other flaviviruses, this results in cross-reactive antibodies which confounds serological interpretations.Methods Plasma from Singapore ZIKV patients was screened longitudinally for antibody responses and neutralizing capacities against ZIKV. Samples from healthy controls, ZIKV and DENV patients were further assessed using ZIKV and DENV peptides of precursor membrane (prM), envelope (E) or non-structural 1 (NS1) viral proteins in a peptide-based ELISA for epitope identification. Identified epitopes were re-validated and diagnostically evaluated using sera of patients with DENV, bacteria or unknown infections from Thailand.Results Long-lasting ZIKV-neutralizing antibodies were elicited during ZIKV infection. Thirteen potential linear B-cell epitopes were identified and of these, four common flavivirus, three ZIKV-specific, and one DENV-specific differential epitopes had more than 50% sensitivities and specificities. Notably, ZIKV-specific peptide 26 on domain I/II of E protein (amino acid residues 271-288) presented 80% sensitivity and 85.7% specificity. Importantly, the differential epitopes also showed significance in differentiating non-flavivirus patient samples.Conclusions Linear B-cell epitope candidates to differentiate ZIKV and DENV infections were identified, providing the first step towards the design of a much-needed serology-based assay.