CWB is promising for treating EVD in resource-poor settings, especially in the early phases of outbreaks when resource-mobilization is done. Even though our sample size was small and the evaluation was not randomised, our results contribute to existing evidence that convalescent whole blood could be considered as a useful candidate for treating EVD. Further studies that are randomised will be required to further assess the efficacy of CWB as treatment option during any EVD outbreak.

No abstract

No abstract

BACKGROUNDPassive therapy with convalescent plasma provides an early opportunity to intervene in Ebola virus disease (EVD). Methods for field screening and selection of potential donors and quantifying plasma antibody are needed.STUDY DESIGN AND METHODSRecombinant Ebola virus glycoprotein (EBOV GP) was formatted into immunoglobulin G‐capture, competitive, and double‐antigen bridging enzyme immunoassays (EIAs). EVD survivors in Freetown, Sierra Leone, were recruited as potential plasma donors and assessed locally using sera alone and/or paired sera and oral fluids (ORFs). Uninfected controls comprised unexposed Gambians and communities in Western Area, Sierra Leone. Antibody neutralization in selected sera was measured retrospectively in a pseudotype virus assay.RESULTSA total of 115 potential donors were considered for enrollment: 110 plasma samples were concordantly reactive in the three EIAs; three were concordantly unreactive and two were reactive in two of three EIAs (98.2% agreement; 95% confidence interval [CI], 93.9%‐99.8%). In 88 donors with paired ORF and plasma, G‐capture EIA reactivity correlated well in the two analytes (R2 = 0.795). Plasma and ORF from 44 Gambians were unreactive. ORF samples from 338 of 339 unexposed Western Area community controls were unreactive (specificity, 99.7%; 95% CI, 98.4%‐99.7%); ORF samples from 113 of 116 Kerry Town EVD survivors were reactive (sensitivity, 97.4%; 95% CI, 92.5%‐99.5%). Strong reactivity in G‐capture and/or competitive EIAs identified donors with high plasma EBOV GP antibody levels in the double‐antigen bridging assay, correlating with high levels of neutralizing antibody.CONCLUSIONSIn‐field testing can qualify convalescent donors for providing high‐titer antibody.

Neutralizing antibody function provides a foundation for the efficacy of vaccines and therapies [1][2][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.Limited EBOV outbreaks have been recorded since 1976 1 . The much larger 2013-2016 West African epidemic (28,610 cases) and the ongoing 2018 Eastern Zaire outbreak (3,188 cases as of September 2019) (https://www.who.int/emergencies/diseases/Ebola/drc-2019) in the Democratic Republic of the Congo (DRC) have been more extensive. These larger outbreaks have indicated that the virus can persist in some individuals, with the potential for subsequent viral transmission 2 . Because the number of Ebola outbreaks has been small, we have limited understanding of natural induced immune responses, and our knowledge of vaccine-induced responses comes largely from animal models 3 . These models have indicated that total levels of IgG-binding antibodies can correlate with protection and with neutralizing antibody (nAb) responses, which can typically be low.Outbreaks in humans have provided valuable information regarding therapeutic 4 and vaccine intervention strategies [5][6][7] for EBOV. More recently, nAbs have been the focus of therapeutic development [8][9][10][11][12] . A cocktail of monoclonal antibodies (mAbs) was administered during the 2013-2016 outbreak 12,13 , and trials conducted in the DRC showed evidence of efficacy 14 . In early 2015, two related studies (Ebola-Tx 15 and Ebola-CP 16 ) were established to recruit apparently health survivors of EBOV with the intent of using their convalescent plasma (CP) to treat disease 4,16,17 . We used CP from the donors of the Ebola-CP study (Supplementary Table 1a), in which samples were collected longitudinally (30-500 days) to better ascertain how...