Evaluation of eight commercial Zika virus IgM and IgG serology assays for diagnostics and research

Abstract

Several commercial Zika virus (ZIKV) serology assays have been developed since the recognition of ZIKV outbreaks as a Public Health Emergency of International Concern in 2016. However, test interpretation for ZIKV serology can be challenging due to antibody cross-reactivity with other flaviviruses like dengue virus (DENV). Therefore, we sought to evaluate the performance of eight commercially available ZIKV IgM and IgG assays across three testing platforms, namely, immunochromatographic tests (ICT), ELISAs and immunofluorescence tests (IIFT). The test panel comprised of 278 samples, including acute and convalescent sera or plasma from ZIKV-confirmed, DENV-confirmed, non-ZIKV and non-DENV patients, and residual sera from healthy blood donors. The ZIKV IgM and IgG serology assays yielded higher test sensitivities of 23.5% - 97.1% among ZIKV convalescent samples as compared to 5.6% - 27.8% among ZIKV acute samples; the test specificities were 63.3% - 100% among acute and convalescent DENV, non-DENV samples. Among the ELISAs and IIFTs, the Diapro ZIKV IgM ELISA demonstrated high test sensitivity (96%) and specificity (80%) when tested on early convalescent samples, while the Euroimmun ZIKV IgG ELISA yielded the highest test specificity of 97% - 100% on samples from non-ZIKV patients and healthy blood donors. For rapid ICTs, the LumiQuick IgM rapid ICT yielded low test sensitivity, suggesting its limited utility. We showed that commercial ZIKV IgM and IgG serology assays have differing test performances, with some having moderate to high test sensitivities and specificities when used in a dengue endemic setting, although there were limitations in IgG serology.

Zika a Vector Borne Disease Detected in Newer States of India Amidst the COVID-19 Pandemic

“…All the four patients with IgM positivity had reported onset of illness within 4-5 days. This matches with the published literature where IgM antibodies for ZIKV have been reported as early as within 4 days of onset of illness (Landry and St George, 2017;Silva et al, 2020;Low et al, 2021). We could not test more positive or negative samples for ZIKV IgM and PRNT due to the limitation in sample volumes received from various VRDLs for retrospective screening.…”

“…While seven sequences of the DENV-4 clustered with sequences from Tamil Nadu and belonged to genotype I (Figures 4A-D). Of the CHIKV positive samples, the Ct range was higher (Asadi-Pooya, 2016;Warrier and Ashokan, 2016;Landry and St George, 2017;Lina Villa et al, 2017;Liu et al, 2017;Ward et al, 2018;Yadav et al, 2018Yadav et al, , 2020Freitas et al, 2020;Malhotra et al, 2020;Silva et al, 2020;Low et al, 2021;Stiasny et al, 2021) and NGS could not lead to giving useful sequences to be used for analysis. The amino acid changes in the NS5 protein of DENV-1-DENV-4 observed with respect to its reference are depicted in Supplementary Figures 2, 5 respectively.…”

Dynamics of the Magnitude, Breadth and Depth of the Antibody Response at Epitope Level Following Dengue Infection

“…non-structural 1 (NS1), E protein, domain III of E (EDIII)]. These second-generation assays show promising results because of improved specificity (26)(27)(28), but do not completely resolve the issue of cross-reactivity (25,29). Probably, this is because individual homologous proteins from different flaviviruses still present discrete conserved immunodominant regions with high similarity that are recognized by CR-Abs (5,25,30).…”

Visualization of Zika Virus Infection via a Light-Initiated Bio-Orthogonal Cycloaddition Labeling Strategy

“…Recent outbreaks of ZIKV have been reported in more than 30 countries or territories, emerging as a major threat to global health (Sampathkumar and Sanchez, 2016;Hills et al, 2017;Mengesha Tsegaye et al, 2018). The current diagnostic techniques available for ZIKV rely on the reverse transcriptase-polymerase chain reaction assay or ZIKV-specific IgM antibody testing, which play an important role in preventing the spread of disease (Ergünay et al, 2010;Barreiro, 2016;Kikuti et al, 2018;Low et al, 2021). The exploration of cellular signaling pathways on ZIKV infection has also attracted considerable research attention, greatly enriching the study of mechanisms of infection of RNA viruses (Grant et al, 2016;Chen et al, 2018;Chiramel and Best, 2018;Garcia et al, 2020).…”