Dataset Information

SARS-CoV-2 neutralising antibody testing in Europe: towards harmonisation of neutralising antibody titres for better use of convalescent plasma and comparability of trial data.

ABSTRACT: We compared the performance of SARS-CoV-2 neutralising antibody testing between 12 European laboratories involved in convalescent plasma trials. Raw titres differed almost 100-fold differences between laboratories when blind-testing 15 plasma samples. Calibration of titres in relation to the reference reagent and standard curve obtained by testing a dilution series reduced the inter-laboratory variability ca 10-fold. The harmonisation of neutralising antibody quantification is a vital step towards determining the protective and therapeutic levels of neutralising antibodies.

SUBMITTER: Nguyen D

PROVIDER: S-EPMC8268650 | biostudies-literature | 2021 Jul

REPOSITORIES: biostudies-literature

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SARS-CoV-2 neutralising antibody testing in Europe: towards harmonisation of neutralising antibody titres for better use of convalescent plasma and comparability of trial data.

Nguyen Dung D Simmonds Peter P Steenhuis Maurice M Wouters Elise E Desmecht Daniel D Garigliany Mutien M Romano Marta M Barbezange Cyril C Maes Piet P Van Holm Bram B Mendoza Joaquín J Oyonarte Salvador S Fomsgaard Anders A Lassaunière Ria R Zusinaite Eva E Resman Rus Katarina K Avšič-Županc Tatjana T Reimerink Johan Hj JH Brouwer Fiona F Hoogerwerf Marieke M Reusken Chantal Bem CB Grodeland Gunnveig G Le Cam Sophie S Gallian Pierre P Amroun Abdennour A Brisbarre Nadège N Martinaud Christophe C Leparc Goffart Isabelle I Schrezenmeier Hubert H Feys Hendrik B HB van der Schoot C Ellen CE Harvala Heli H

Euro surveillance : bulletin Europeen sur les maladies transmissibles = European communicable disease bulletin 20210701 27

We compared the performance of SARS-CoV-2 neutralising antibody testing between 12 European laboratories involved in convalescent plasma trials. Raw titres differed almost 100-fold differences between laboratories when blind-testing 15 plasma samples. Calibration of titres in relation to the reference reagent and standard curve obtained by testing a dilution series reduced the inter-laboratory variability ca 10-fold. The harmonisation of neutralising antibody quantification is a vital step towar ...[more]

PMID: 34240697

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Project description:BackgroundSeveral SARS-CoV-2 variants of concern have been identified that partly escape serum neutralisation elicited by current vaccines. Studies have also shown that vaccines demonstrate reduced protection against symptomatic infection with SARS-CoV-2 variants. We explored whether in-vitro neutralisation titres remain predictive of vaccine protection from infection with SARS-CoV-2 variants.MethodsIn this meta-analysis, we analysed published data from 24 identified studies on in-vitro neutralisation and clinical protection to understand the loss of neutralisation to existing SARS-CoV-2 variants of concern. We integrated the results of this analysis into our existing statistical model relating in-vitro neutralisation to protection (parameterised on data from ancestral virus infection) to estimate vaccine efficacy against SARS-CoV-2 variants. We also analysed data on boosting of vaccine responses and use the model to predict the impact of booster vaccination on protection against SARS-CoV-2 variants.FindingsThe neutralising activity against the ancestral SARS-CoV-2 was highly predictive of neutralisation of variants of concern. Decreases in neutralisation titre to the alpha (1·6-fold), beta (8·8-fold), gamma (3·5-fold), and delta (3·9-fold) variants (compared to the ancestral virus) were not significantly different between different vaccines. Neutralisation remained strongly correlated with protection from symptomatic infection with SARS-CoV-2 variants of concern (r S=0·81, p=0·0005) and the existing model remained predictive of vaccine efficacy against variants of concern once decreases in neutralisation to the variants of concern were incorporated. Modelling of predicted vaccine efficacy against variants over time suggested that protection against symptomatic infection might decrease below 50% within the first year after vaccination for some vaccines. Boosting of previously infected individuals with existing vaccines (which target ancestral virus) is predicted to provide a higher degree of protection from infection with variants of concern than primary vaccination schedules alone.InterpretationIn-vitro neutralisation titres remain a correlate of protection from SARS-CoV-2 variants and modelling of the effects of waning immunity predicts a loss of protection to the variants after vaccination. However, booster vaccination with current vaccines should enable higher neutralisation to SARS-CoV-2 variants than is achieved with primary vaccination, which is predicted to provide robust protection from severe infection outcomes with the current SARS-CoV-2 variants of concern, at least in the medium term.FundingThe National Health and Medical Research Council (Australia), the Medical Research Future Fund (Australia), and the Victorian Government.

Project description:IntroductionThe lack of approved specific therapeutic agents to treat coronavirus disease (COVID-19) associated with severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infection has led to the rapid implementation of convalescent plasma therapy (CPT) trials in many countries, including the United Kingdom. Effective CPT is likely to require high titres of neutralising antibody (nAb) in convalescent donations. Understanding the relationship between functional neutralising antibodies and antibody levels to specific SARS-CoV-2 proteins in scalable assays will be crucial for the success of a large-scale collection. We assessed whether neutralising antibody titres correlated with reactivity in a range of enzyme-linked immunosorbent assays (ELISA) targeting the spike (S) protein, the main target for human immune response.MethodsBlood samples were collected from 52 individuals with a previous laboratory-confirmed SARS-CoV-2 infection. These were assayed for SARS-CoV-2 nAbs by microneutralisation and pseudo-type assays and for antibodies by four different ELISAs. Receiver operating characteristic (ROC) analysis was used to further identify sensitivity and specificity of selected assays to identify samples containing high nAb levels.ResultsAll samples contained SARS-CoV-2 antibodies, whereas neutralising antibody titres of greater than 1:20 were detected in 43 samples (83% of those tested) and >1:100 in 22 samples (42%). The best correlations were observed with EUROimmun immunoglobulin G (IgG) reactivity (Spearman Rho correlation coefficient 0.88; p < 0.001). Based on ROC analysis, EUROimmun would detect 60% of samples with titres of >1:100 with 100% specificity using a reactivity index of 9.1 (13/22).DiscussionRobust associations between nAb titres and reactivity in several ELISA-based antibody tests demonstrate their possible utility for scaled-up production of convalescent plasma containing potentially therapeutic levels of anti-SARS-CoV-2 nAbs.

Dataset Information

SARS-CoV-2 neutralising antibody testing in Europe: towards harmonisation of neutralising antibody titres for better use of convalescent plasma and comparability of trial data.

Publications

SARS-CoV-2 neutralising antibody testing in Europe: towards harmonisation of neutralising antibody titres for better use of convalescent plasma and comparability of trial data.

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