Abstract
The specificity of the antibody response against Zika virus (ZIKV) is not well-characterized. This is due, in part, to the antigenic similarity between ZIKV and closely related dengue virus (DENV) serotypes. Since these and other similar viruses co-circulate, are spread by the same mosquito species, and can cause similar acute clinical syndromes, it is difficult to disentangle ZIKV-specific antibody responses from responses to closely-related arboviruses in humans. Here we use high-density peptide microarrays to profile anti-ZIKV antibody reactivity in pregnant and non-pregnant macaque monkeys with known exposure histories and compare these results to reactivity following DENV infection. We also compare cross-reactive binding of ZIKV-immune sera to the full proteomes of 28 arboviruses. We independently confirm a purported ZIKV-specific IgG antibody response targeting ZIKV nonstructural protein 2B (NS2B) that was recently reported in ZIKV-infected people and we show that antibody reactivity in pregnant animals can be detected as late as 127 days post-infection (dpi). However, we also show that these responses wane over time, sometimes rapidly, and in one case the response was elicited following DENV infection in a previously ZIKV-exposed animal. These results suggest epidemiologic studies assessing seroprevalence of ZIKV immunity using linear epitope-based strategies will remain challenging to interpret due to susceptibility to false positive results. However, the method used here demonstrates the potential for rapid profiling of proteome-wide antibody responses to a myriad of neglected diseases simultaneously and may be especially useful for distinguishing antibody reactivity among closely related pathogens.
Highlights
Serologic assays designed to detect Zika virus (ZIKV) infection suffer from cross-reactivity with antibodies to closely related dengue virus (DENV), due to the high level of amino acid sequence identity and structural similarity [1,2,3,4] between the two viruses
We show that while ZIKV-specific antibody binding can be detected, these responses are generally weak and ephemeral, and false positives may arise through DENV infection
We synthesized linear 16-mer peptides, overlapping by 12 amino acids, representing the SIVmac239 envelope protein and analyzed serum from two Mauritian cynomolgus macaques for simian immunodeficiency virus (SIV)-specific IgG reactivity before and approximately 125 days after SIVmac239 infection (Table 1). (We have previously plotted data procured from peptide array assays of these samples [38] while investigating the antibody response to SIV in the context of simian pegivirus infection; here we show the same data using the updated, improved data processing pipeline described above.) Post-infection samples showed fluorescence intensity as high as 1,000 times the intensity in pre-infection samples (S1 Fig)
Summary
Serologic assays designed to detect Zika virus (ZIKV) infection suffer from cross-reactivity with antibodies to closely related dengue virus (DENV), due to the high level of amino acid sequence identity (average ~55%) and structural similarity [1,2,3,4] between the two viruses. Serologic assays have been developed to detect past ZIKV infection, reporting sensitivity varying from 37% to 97% and specificity varying from 20% to 90% [5,6,7,8]. A recent publication by Mishra et al employed a high-density peptide microarray to identify antibodies to linear ZIKV epitopes lacking crossreactivity with other flaviviruses [13]. This group identified an IgG immunoreactive peptide sequence in the ZIKV nonstructural protein 2B (NS2B) which induced little antibody binding in serum from ZIKV-naive people and was bound in early convalescence in most cases of symptomatic ZIKV infection [13]. This group did note seropositivity in a ZIKV-naive, DENVimmune individual and in one individual with no known flavivirus infection history
Sign-in/Register to view highlights & summary Talk to us
Join us for a 30 min session where you can share your feedback and ask us any queries you have
Schedule a callDisclaimer: All third-party content on this website/platform is and will remain the property of their respective owners and is provided on "as is" basis without any warranties, express or implied. Use of third-party content does not indicate any affiliation, sponsorship with or endorsement by them. Any references to third-party content is to identify the corresponding services and shall be considered fair use under The CopyrightLaw.
