Anti-Ebola Virus Antibody Levels in Convalescent Plasma and Viral Load After Plasma Infusion in Patients With Ebola Virus Disease

Abstract

Background: Ebola virus (EBOV) neutralizing antibody in plasma may reduce viral load following administration of plasma to patients with Ebola virus disease (EVD), but measurement of these antibodies is complex.

Methods: Anti-EBOV antibody was measured by 2 neutralization and 2 enzyme-linked immunosorbent assays (ELISAs) in convalescent plasma (ECP) from 100 EVD survivor donors in Liberia. Viral load was assessed repetitively in patients with EVD participating in a clinical trial of enhanced standard of care plus ECP.

Results: All 4 anti-EBOV assays were highly concordant for detection of EBOV antibody. Antibodies were not detected in plasma specimens obtained from 15 of 100 donors, including 7 with documented EBOV-positive reverse-transcription polymerase chain reaction during EVD. Viral load was reduced following each dose in the 2 clinical trial participants who received ECP with higher antibody levels but not in the 2 who received ECP with lower antibody levels.

Conclusions: Recovery from EVD can occur with absence of detectable anti-EBOV antibody several months after disease onset. ELISAs may be useful to select ECP donors or identify ECP units that contain neutralizing antibody. ECP with higher anti-EBOV antibody levels may have greater effect on EBOV load-an observation that requires further investigation.

Clinical trials registration: NCT02333578.

Figures

Figure 1.

A and B, Distributions of anti-Ebola virus (EBOV) and EBOV glycoprotein (GP) enzyme-linked immunosorbent assay (ELISA) values from the first 100 specimens according to their 50% plaque reduction neutralization test (PRNT50) titer. The first blood specimen collected from each plasma donor was assayed by immunoglobulin G (IgG) EBOV ELISA, IgG EBOV GP ELISA, and PRNT50. ELISA units per milliliter in each specimen were derived using a standard curve prepared with a reference antibody. Open circles depict ELISA results at each PRNT50 titer. Open horizontal bars denote median ELISA values. Dotted line indicates upper cutoff for negative ELISA values.

Figure 2.

A–D, Ebola virus (EBOV) load in participants treated with Ebola convalescent plasma. Participants were treated with enhanced standard of care. In addition, Ebola convalescent plasma was infused (vertical lines) within 4 hours after collection of preinfusion blood specimens for viral load. Specimens obtained at the time points indicated (squares) were assayed for EBOV by reverse-transcription polymerase chain reaction and converted to log10 genomic equivalents/mL by a formula established at assay validation. Dashed line indicates lower limit of virus detection. Zero hours indicates time of first preinfusion specimen collection.

Figure 3.

A and B, Ebola virus (EBOV) load in control participants. Participants were treated with enhanced standard of care. Blood specimens obtained at the time points indicated (squares) were assayed for EBOV by reverse-transcription polymerase chain reaction and converted to log10 genomic equivalents per milliliter by a formula established at assay validation. Dashed line indicates lower limit of virus detection. Zero hours indicates time of first specimen collection after enrollment.