Antibody responses to Zika virus proteins in pregnant and non-pregnant macaques

PLoS Negl Trop Dis. 2018 Nov 27;12(11):e0006903. doi: 10.1371/journal.pntd.0006903. eCollection 2018 Nov.


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.

Publication types

  • Research Support, N.I.H., Extramural
  • Research Support, Non-U.S. Gov't

MeSH terms

  • Animals
  • Antibodies, Viral / blood
  • Antibodies, Viral / immunology*
  • Antibody Formation
  • Cross Reactions
  • Epitope Mapping
  • Epitopes / chemistry
  • Epitopes / genetics
  • Epitopes / immunology
  • Female
  • Humans
  • Macaca
  • Male
  • Pregnancy
  • Pregnancy Complications / blood
  • Pregnancy Complications / immunology*
  • Pregnancy Complications / virology
  • Seroepidemiologic Studies
  • Viral Nonstructural Proteins / chemistry
  • Viral Nonstructural Proteins / genetics
  • Viral Nonstructural Proteins / immunology*
  • Zika Virus / chemistry
  • Zika Virus / genetics
  • Zika Virus / immunology*
  • Zika Virus / isolation & purification
  • Zika Virus Infection / blood
  • Zika Virus Infection / immunology*
  • Zika Virus Infection / virology


  • Antibodies, Viral
  • Epitopes
  • NS2B protein, flavivirus
  • Viral Nonstructural Proteins