Analysis of Memory Antibody Responses in Individuals with Zika-Associated Guillain-Barré Syndrome

Viruses. 2024 Oct 30;16(11):1704. doi: 10.3390/v16111704.

Abstract

The Zika virus (ZIKV) was responsible for a major outbreak in 2015 in the Americas. Infections were associated with increased cases of microcephaly in infants and Guillain-Barré Syndrome (GBS) in adults. Our group previously demonstrated that Zika-associated GBS correlated with the increased neutralization of ZIKV and DENV2, but the antibody specificity was not analyzed. Here, we generated reporter virus particles (RVPs) of ZIKV with specific-point mutations that allowed us to investigate the specificity of circulating plasma antibodies at two different timepoints from individuals with Zika-associated GBS. We found that neutralizing antibody titers to ZIKV waned between one and two years post-ZIKV infection in GBS-negative but not GBS-positive individuals. Interestingly, plasma neutralization by GBS-negative individuals was more sensitive to a mutation at position N154A than plasma from GBS-positive individuals. To determine if waning was associated with different levels of B-cell activation at the time of infection, pro-inflammatory cytokines were measured, but no differences were observed in people with or without GBS. These data suggest subtle differences between GBS-positive and-negative individuals' circulating antibodies, where antibodies from GBS-positive individuals may target different epitopes and remain in circulation longer as compared to GBS-negative individuals.

Keywords: Dengue; E dimer epitope; Guillain–Barré Syndrome; N154A; Zika; glycan; neutralizing antibodies; pro-inflammatory cytokines.

MeSH terms

  • Adult
  • Antibodies, Neutralizing* / blood
  • Antibodies, Neutralizing* / immunology
  • Antibodies, Viral* / blood
  • Antibodies, Viral* / immunology
  • Antibody Formation
  • B-Lymphocytes / immunology
  • Female
  • Guillain-Barre Syndrome* / immunology
  • Guillain-Barre Syndrome* / virology
  • Humans
  • Immunologic Memory
  • Male
  • Zika Virus Infection* / complications
  • Zika Virus Infection* / immunology
  • Zika Virus Infection* / virology
  • Zika Virus* / immunology

Substances

  • Antibodies, Viral
  • Antibodies, Neutralizing