Standardised neutralising antibody assays are needed for evaluating COVID-19 vaccines

Wang, Youchun

doi:10.1016/j.ebiom.2021.103677

Cited by 6 publications

(7 citation statements)

References 10 publications

(8 reference statements)

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“…Live-virus plaque reduction neutralization tests (PRNT), considered the gold standard for measuring Nabs, are cumbersome, expensive and require a biosafety level (BSL) 3 laboratory environment. Furthermore, these assays have suboptimal interlaboratory reproducibility as there is no standardized protocol that is universally used ( 14 – 16 ). As an alternative to PRNT, the correlation of antibodies directed against the spike RBD measured with routine laboratory assays (“binding” antibodies) could in theory be used to infer protection ( 12 ).…”

Section: Introductionmentioning

confidence: 99%

IgG Anti-Spike Antibodies and Surrogate Neutralizing Antibody Levels Decline Faster 3 to 10 Months After BNT162b2 Vaccination Than After SARS-CoV-2 Infection in Healthcare Workers

et al. 2022

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BackgroundIgG anti-spike (S) antibodies arise after SARS-CoV-2 infection as well as vaccination. Levels of IgG anti-S are linked to neutralizing antibody titers and protection against (re)infection.MethodsWe measured IgG anti-S and surrogate neutralizing antibody kinetics against Wild Type (WT) and 4 Variants of Concern (VOC) in health care workers (HCW) 3 and 10 months after natural infection (“infection”, n=83) or vaccination (2 doses of BNT162b2) with (“hybrid immunity”, n=17) or without prior SARS-CoV-2 infection (“vaccination”, n=97).ResultsThe humoral immune response in the “vaccination” cohort was higher at 3 months, but lower at 10 months, compared to the “infection” cohort due to a faster decline. The “hybrid immunity” cohort had the highest antibody levels at 3 and 10 months with a slower decline compared to the “vaccination” cohort. Surrogate neutralizing antibody levels (expressed as %inhibition of ACE-2 binding) showed a linear relation with log10 of IgG anti-S against WT and four VOC. IgG anti-S corresponding to 90% inhibition ranged from 489 BAU/mL for WT to 1756 BAU/mL for Beta variant. Broad pseudoneutralization predicted live virus neutralization of Omicron BA.1 in 20 randomly selected high titer samples.ConclusionsHybrid immunity resulted in the strongest humoral immune response. Antibodies induced by natural infection decreased more slowly than after vaccination, resulting in higher antibody levels at 10 months compared to vaccinated HCW without prior infection. There was a linear relationship between surrogate neutralizing activity and log10 IgG anti-S for WT and 4 VOC, although some VOC showed reduced sensitivity to pseudoneutralization.

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Section: Introductionmentioning

confidence: 99%

IgG Anti-Spike Antibodies and Surrogate Neutralizing Antibody Levels Decline Faster 3 to 10 Months After BNT162b2 Vaccination Than After SARS-CoV-2 Infection in Healthcare Workers

et al. 2022

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“…The measurement of anti-RBD-S1 IgG titers and assumption of 50% vaccine efficacy relied on the wild-type SARS-CoV-2 strain, which could not account for the high evasive capacity of subsequent Omicron VOC spread 38 , 39 . In this regard, the use of an assay for neutralizing activity of vaccine-induced antibody levels would have been optimal, but procedural constraints prevented us from implementing this method of investigation 40 . Finally, although we found a significant difference in the clinical outcome of vaccination, the rate of breakthrough infections is still too low (< 4%).…”

Section: Discussionmentioning

confidence: 99%

Dynamic changes in peripheral lymphocytes and antibody response following a third dose of SARS-CoV-2 mRNA-BNT162b2 vaccine in cancer patients

Ruggeri

Nelli

Giannarelli

et al. 2022

Sci Rep

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The aim of this study was to evaluate the association of circulating lymphocytes profiling with antibody response in cancer patients receiving the third dose of COVID-19 mRNA-BNT162b2 vaccine. Immunophenotyping of peripheral blood was used to determine absolute counts of lymphocyte subsets, alongside detection of IgG antibodies against receptor-binding-domain (RBD) of the SARS-CoV-2 Spike protein (S1) before booster dosing (timepoint-1) and four weeks afterward (timepoint-2). An IgG titer ≥ 50 AU/mL defined a positive seroconversion response. An IgG titer ≥ 4446 AU/mL was assumed as a correlate of 50% vaccine efficacy against symptomatic infections. A total of 258 patients on active treatment within the previous six months were enrolled between September 23 and October 7, 2021. The third dose resulted in an exponential increase in median anti-RBD-S1 IgG titer (P < 0.001), seroconversion rates (P < 0.001), and 50% vaccine efficacy rates (P < 0.001). According to ROC curve analysis, T helper and B cells were significantly associated with seroconversion responses at timepoint-1, whereas only B cells were relevant to 50% vaccine efficacy rates at timepoint-2. A positive linear correlation was shown between anti-RBD-S1 IgG titers and these lymphocyte subset counts. Multivariate analysis ruled out a potential role of T helper cells but confirmed a significant interaction between higher B cell levels and improved antibody response. These findings suggest that peripheral counts of B cells correlate with humoral response to the third dose of mRNA-BNT162b2 vaccine in actively treated cancer patients and could provide insights into a more comprehensive assessment of vaccination efficacy.

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“…In order to better understand the association among humoral response markers and protection from infection an effort in the harmonization of the results obtained from different laboratories worldwide is needed [12]. Indeed, in the current pandemic a large number of serological tests, based on different technologies and recognizing different epitopes of the S-protein, have been used along with neutralization assays.…”

Section: Introductionmentioning

confidence: 99%

Differential Dynamics of SARS-CoV-2 Binding and Functional Antibodies upon BNT162b2 Vaccine: A 6-Month Follow-Up

Matusali

Sberna

Meschi

et al. 2022

Viruses

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To investigate the dynamic association among binding and functional antibodies in health-care-workers receiving two doses of BNT162b2 mRNA COVID-19-vaccine, SARS-CoV-2 anti-RBD IgG, anti-Trimeric-S IgG, and neutralizing antibodies (Nabs) were measured in serum samples collected at 2 weeks, 3 months, and 6 months from full vaccination. Despite the high correlation, results for anti-RBD and anti-Trimeric S IgG were numerically different even after recalculation to BAU/mL following WHO standards indications. Moreover, after a peak response at 2 weeks, anti-RBD IgG levels showed a 4.5 and 13 fold decrease at 3 and 6 months, respectively, while the anti-Trimeric S IgG presented a less pronounced decay of 2.8 and 4.7 fold. Further different dynamics were observed for Nabs titers, resulting comparable at 3 and 6 months from vaccination. We also demonstrated that at NAbs titers ≥40, the area under the receiver operating characteristic curve and the optimal cutoff point decreased with time from vaccination for both anti-RBD and anti-Trimeric S IgG. The mutating relation among the anti-RBD IgG, anti-Trimeric S IgG, and neutralizing antibodies are indicative of antibody maturation upon vaccination. The lack of standardized laboratory procedures is one factor interfering with the definition of a correlate of protection from COVID-19.

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Standardised neutralising antibody assays are needed for evaluating COVID-19 vaccines

Cited by 6 publications

References 10 publications

IgG Anti-Spike Antibodies and Surrogate Neutralizing Antibody Levels Decline Faster 3 to 10 Months After BNT162b2 Vaccination Than After SARS-CoV-2 Infection in Healthcare Workers

IgG Anti-Spike Antibodies and Surrogate Neutralizing Antibody Levels Decline Faster 3 to 10 Months After BNT162b2 Vaccination Than After SARS-CoV-2 Infection in Healthcare Workers

Dynamic changes in peripheral lymphocytes and antibody response following a third dose of SARS-CoV-2 mRNA-BNT162b2 vaccine in cancer patients

Differential Dynamics of SARS-CoV-2 Binding and Functional Antibodies upon BNT162b2 Vaccine: A 6-Month Follow-Up

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