Ebola virus antibody decay-stimulation in a high proportion of survivors

Neutralizing antibody function provides a foundation for the efficacy of vaccines and therapies(1-3). Here, using a robust in vitro Ebola virus (EBOV) pseudo-particle infection assay and a well-defined set of solid-phase assays, we describe a wide spectrum of antibody responses in a cohort of healthy survivors of the Sierra Leone EBOV outbreak of 2013-2016. Pseudo-particle virus-neutralizing antibodies correlated with total anti-EBOV reactivity and neutralizing antibodies against live EBOV. Variant EBOV glycoproteins (1995 and 2014 strains) were similarly neutralized. During longitudinal follow-up, antibody responses fluctuated in a 'decay-stimulation-decay' pattern that suggests de novo restimulation by EBOV antigens after recovery. A pharmacodynamic model of antibody reactivity identified a decay half-life of 77-100 days and a doubling time of 46-86 days in a high proportion of survivors. The highest antibody reactivity was observed around 200 days after an individual had recovered. The model suggests that EBOV antibody reactivity declines over 0.5-2 years after recovery. In a high proportion of healthy survivors, antibody responses undergo rapid restimulation. Vigilant follow-up of survivors and possible elective de novo antigenic stimulation by vaccine immunization should be considered in order to prevent EBOV viral recrudescence in recovering individuals and thereby to mitigate the potential risk of reseeding an outbreak.

Automated summary

Neutralizing antibody function is crucial for vaccine and therapy efficacy. In this study, a wide spectrum of antibody responses in healthy survivors of the Sierra Leone EBOV outbreak was described, with pseudo-particle virus-neutralizing antibodies correlating with total anti-EBOV reactivity. A pharmacodynamic model identified a decay half-life and doubling time in survivors, suggesting that EBOV antibody reactivity declines over time after recovery. Vigilant follow-up and possible vaccine immunization for de novo antigenic stimulation should be considered to prevent EBOV viral recrudescence in recovering individuals.