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

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
• Zika
• Guillain–Barré Syndrome
• neutralizing antibodies
• pro-inflammatory cytokines
• E dimer epitope