Comparison of platform technologies for assaying antibody to Ebola virus

Abstract

BackgroundThe recent Ebola outbreak in West Africa led to the use of a variety of different platform technologies for assaying antibodies because of the difficulties of handling the live virus. The same types of method could be applied rapidly to other infections when they emerge. There is a need to compare quantitative results of different assays, which means that the assays must measure similar parameters and give comparable results.MethodsA collaborative study was carried out to establish an International Reference Reagent through WHO. Nine samples were sent to 16 laboratories and the results from 22 different assays compared to those obtained by neutralisation assays using the wild type virus.FindingsQuantitative correlation with the wild type neutralisation assays was very variable but generally poor, with only five of the twenty-two assays giving a correlation coefficient of 0.7 or greater; the five best assays included methods based on wild type and VSV pseudotype neutralisation and ELISA. They could be applicable to other rapidly emerging diseases. The remaining assays including neutralisation of lentiviral pseudotypes need further development.InterpretationThe assay platform should be chosen with care to ensure that it is fit for purpose. Many of the assays were not suitable for quantitation of antibody levels, a finding that is not surprising given the urgency with which they had to be implemented but some may be of generic value. Antibody titres in samples from a vaccine trial were comparable to those from convalescent patients or lower.FundingFunding was from the UK DoH and the Wellcome Tust.

Detection, characterization, and enrollment of donors of Ebola convalescent plasma in Sierra Leone

“…Quantification of antibody to EBOV GP in DABA correlated with the measurement of biologically determined neutralizing antibody. Both assays also ranked the two WHO standards in the expected order of potency and the observed neutralization IC 50 titers were in agreement with published data . We believe that these observations indicate that the DABA EIA was suitable for quantifying biologically active antibody in the field.…”

“…Both assays also ranked the two WHO standards in the expected order of potency and the observed neutralization IC 50 titers were in agreement with published data. 20 We believe that these observations indicate that the DABA EIA was suitable for quantifying biologically active antibody in the field. If the effect of CP depends on antibody dosing, 10 it will be interesting to quantify neutralizing antibody in the full cohort of Sierra Leone donors.…”

Safety and immunogenicity of the rVSV∆G-ZEBOV-GP Ebola virus vaccine candidate in healthy adults: a phase 1b randomised, multicentre, double-blind, placebo-controlled, dose-response study

“…A comparison of platform technologies for assaying antibodies to Ebola showed substantial differences in neutralisation results in different assays. 26 This study has some limitations. First, to compare the incidence of post-injection arthritis and dermatitis across both cohorts and all dose groups, a pre-unblinding review of adverse events led to prospective establishment of broad, sensitive case definitions based on solicited and unsolicited adverse events.…”

Systematic Analysis of Monoclonal Antibodies against Ebola Virus GP Defines Features that Contribute to Protection

“…Disparities in previous antibody-mediated neutralization results could be due to differing experimental conditions and model systems (Davidson et al, 2015; Li et al, 2016; Wilkinson et al, 2017; Wilson et al, 2000). Thus, we characterized the neutralization of each mAb in three assays: i) replication-competent vesicular stomatitis virus bearing EBOV GP (rVSV); ii) biologically contained EBOV (ΔVP30) (Halfmann et al, 2008); and iii) authentic EBOV (Figure 2) performed under BSL-2+, BSL-3 and BSL-4 containment, respectively, as previously described, to ensure consistency with previous studies.…”