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; Simmonds, Peter; Steenhuis, Maurice; Wouters, Elise; Desmecht, Daniël; Garigliany, Mutien; Romano, Márta; Barbezange, Cyril; Maes, Piet; Holm, Bram Van; Mendoza, Joaquín; Oyonarte, S; Fomsgaard, Anders; Lassaunière, Ria; Žusinaite, Eva; Rus, Katarina Resman; Avšič–Županc, Tatjana; Reimerink, Johan; Brouwer, Fiona; Hoogerwerf, Marieke; Reusken, Chantal; Grødeland, Gunnveig; Cam, Sophie Le; Gallian, Pierre; Amroun, Abdennour; Brisbarre, Nadège; Martinaud, Christophe; Goffart, Isabelle Leparc; Schrezenmeier, Hubert; Feys, Hendrik B.; Schoot, C. Ellen van der; Harvala, Heli

doi:10.2807/1560-7917.es.2021.26.27.2100568

Cited by 35 publications

(37 citation statements)

References 16 publications

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“…For the neutralizing antibody testing, a standard live SARS‐CoV‐2 microneutralization assay was used 24 . The assay readout was the cytopathic effect, where the assay cut‐off titer was <1:20.…”

Section: Methodsmentioning

confidence: 99%

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ABO blood group does not influence the level of anti‐SARS‐CoV‐2 antibodies in convalescent plasma donors

et al. 2022

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Background The association of the ABO blood group with COVID‐19 disease has been confirmed by several studies, with the blood group A patients being more susceptible and prone to a more severe clinical course of the disease. Additionally, several authors also addressed the association of ABO‐types and the levels of anti‐SARS‐CoV‐2 antibodies in convalescents, mostly supporting a theory that the non‐O blood group convalescents present with higher levels of anti‐SARS‐CoV‐2 antibodies. Study Design and Methods Since previous findings were based on small convalescent cohorts, we quantified the anti‐SARS‐CoV‐2 antibody levels in a total of 3187 convalescent plasma donors with three commercial serological and one standard neutralizing antibody test. The majority of donors had undergone a mild form of the disease and the median time of sampling was 66 days after diagnosis. Results None of the antibody quantitation results showed any significant association with the ABO blood group types. The same result was evident in the subgroup of vaccinated individuals (n = 370) and the subgroups when stratified according to post‐COVID‐19 periods (0–60, 60–120, and 120–180 days). Conclusion In conclusion, we found no evidence to confirm that the ABO blood group types influence the level of SARS‐CoV‐2 antibody response in COVID‐19 convalescent plasma donors.

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Section: Methodsmentioning

confidence: 99%

“…For the neutralizing antibody testing, a standard live SARS-CoV-2 microneutralization assay was used. 24 The assay readout was the cytopathic effect, where the assay cut-off titer was <1:20. Assay results below the lower limit of quantitation were set to 0.5 times the lower limit of quantitation.…”

Section: Antibody Testingmentioning

confidence: 99%

ABO blood group does not influence the level of anti‐SARS‐CoV‐2 antibodies in convalescent plasma donors

et al. 2022

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“…After 24 h, virus inhibition was measured in a validated in-house anti-SARS-CoV-2 nucleocapsid protein ELISA, following the principle of the World Health Organization influenza microneutralisation protocol [ 12 ]. This SARS-CoV-2 microneutralisation assay has a comparable performance relative to other neutralisation assays used in European laboratories (Laboratory 4 in ref [ 13 ]). The ELISA signal was unaffected by amino acid substitutions present in the nucleocapsid protein of some SARS-CoV-2 isolates.…”

Section: Neutralisation Assaymentioning

confidence: 99%

Neutralisation of the SARS-CoV-2 Delta variant sub-lineages AY.4.2 and B.1.617.2 with the mutation E484K by Comirnaty (BNT162b2 mRNA) vaccine-elicited sera, Denmark, 1 to 26 November 2021

et al. 2021

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Several factors may account for the recent increased spread of the SARS-CoV-2 Delta sub-lineage AY.4.2 in the United Kingdom, Romania, Poland, and Denmark. We evaluated the sensitivity of AY.4.2 to neutralisation by sera from 30 Comirnaty (BNT162b2 mRNA) vaccine recipients in Denmark in November 2021. AY.4.2 neutralisation was comparable to other circulating Delta lineages or sub-lineages. Conversely, the less prevalent B.1.617.2 with E484K showed a significant more than 4-fold reduction in neutralisation that warrants surveillance of strains with the acquired E484K mutation.

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“…There is also evidence that neutralizing titers for SARS-CoV-2wt are predictive of protection against other variants including Delta 3,4 . However, virus neutralization assays are poorly standardized and difficult to scale up 3,5 . Thus, the neutralization titers corresponding to 90% vaccine efficacy against symptomatic COVID-19 varied by more than ten-fold in two clinical trials 1,2 .…”

Section: Introductionmentioning

confidence: 99%

Titers of antibodies the receptor-binding domain (RBD) of ancestral SARS-CoV-2 are predictive for levels of neutralizing antibodies to multiple variants

Tran

Vaage

Mehta

et al. 2022

Preprint

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Diagnostic assays currently used to monitor the efficacy of COVID-19 vaccines measure levels of antibodies to the receptor-binding domain of ancestral SARS-CoV-2 (RBDwt). However, the predictive value for protection against new variants of concern (VOCs) has not been firmly established. Here, we used bead-based arrays and flow cytometry to measure binding of antibodies to spike proteins and receptor-binding domains (RBDs) from VOCs in 12,000 sera. Effects of sera on RBD-ACE2 interactions were measured as a proxy for neutralizing antibodies. The samples were obtained from healthy individuals or patients on immunosuppressive therapy who had received two to four doses of COVID-19 vaccines and from COVID-19 convalescents. The results show that anti-RBDwt titers correlate with the levels of binding- and neutralizing antibodies against the Alpha, Beta, Gamma, Delta, Epsilon and Omicron variants. The benefit of multiplexed analysis lies in the ability to measure a wide range of anti-RBD titers using a single dilution of serum for each assay. The reactivity patterns also yield an internal reference for neutralizing activity and binding antibody units per milliliter (BAU/ml). Results obtained with sera from vaccinated healthy individuals and patients confirmed and extended results from previous studies on time-dependent waning of antibody levels and effects of immunosuppressive agents. We conclude that anti-RBDwt titers correlate with levels of neutralizing antibodies against VOCs and propose that our method may be implemented to enhance the precision and throughput of immunomonitoring.

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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

Cited by 35 publications

References 16 publications

ABO blood group does not influence the level of anti‐SARS‐CoV‐2 antibodies in convalescent plasma donors

ABO blood group does not influence the level of anti‐SARS‐CoV‐2 antibodies in convalescent plasma donors

Neutralisation of the SARS-CoV-2 Delta variant sub-lineages AY.4.2 and B.1.617.2 with the mutation E484K by Comirnaty (BNT162b2 mRNA) vaccine-elicited sera, Denmark, 1 to 26 November 2021

Titers of antibodies the receptor-binding domain (RBD) of ancestral SARS-CoV-2 are predictive for levels of neutralizing antibodies to multiple variants

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