Cohort-specific serological recognition of SARS-CoV-2 variant RBD antigens
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Abstract
Background
Estimating the response of different cohorts (e.g. vaccinated or critically ill) to new SARS-CoV-2 variants is important to customize measures of control. Thus, our goal was to evaluate binding of antibodies from sera of infected and vaccinated people to different antigens expressed by SARS-CoV-2 variants.
Methods
We compared sera from vaccinated donors with sera from four patient/donor cohorts: critically ill patients admitted to an intensive care unit (split in sera collected between 2 and 7 days after admission and more than ten days later), a NIBSC/WHO reference panel of SARS-CoV-2 positive individuals, and ambulatory or hospitalized (but not critically ill) positive donors. Samples were tested with an anti-SARS-CoV-2 IgG serological assay designed with microplates coated with a SARS-CoV-2 RBD recombinant antigen. The same sample sets were also tested with microplates coated with antigens harbouring RBD mutations present in eleven of the most widespread variants.
Results
Sera from vaccinated individuals exhibited higher antibody binding (P<0.001) than sera from infected (but not critically ill) individuals when tested against the WT and each of 11 variants’ RBD.
The optical density generated by sera from non-critically ill convalescence individuals upon binding to variant’s antigens was different (P<0.05) from that of the WT in some variants—noteworthy, Beta, Gamma, Delta, and Delta Plus variants.
Conclusions
Understanding differences in binding and neutralizing antibody titers against WT vs variant RBD antigens from different donor cohorts can help design variant-specific immunoassays and complement other diagnostic and clinical data to evaluate the epidemiology of new variants.
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SciScore for 10.1101/2022.01.10.21268250: (What is this?)
Please note, not all rigor criteria are appropriate for all manuscripts.
Table 1: Rigor
Ethics Consent: , Lampire Biological Laboratories (Pipersville, PA, USA), or Plasma Services Group, Inc (Moorestown, NJ, USA), each of which confirmed patient consent and participation in an Institutional Review Board (IRB) approved protocol.
IRB: , Lampire Biological Laboratories (Pipersville, PA, USA), or Plasma Services Group, Inc (Moorestown, NJ, USA), each of which confirmed patient consent and participation in an Institutional Review Board (IRB) approved protocol.Sex as a biological variable not detected. Randomization not detected. Blinding not detected. Power Analysis not detected. Table 2: Resources
Antibodies Sentences Resources More detailed information about each sample and the demographics, … SciScore for 10.1101/2022.01.10.21268250: (What is this?)
Please note, not all rigor criteria are appropriate for all manuscripts.
Table 1: Rigor
Ethics Consent: , Lampire Biological Laboratories (Pipersville, PA, USA), or Plasma Services Group, Inc (Moorestown, NJ, USA), each of which confirmed patient consent and participation in an Institutional Review Board (IRB) approved protocol.
IRB: , Lampire Biological Laboratories (Pipersville, PA, USA), or Plasma Services Group, Inc (Moorestown, NJ, USA), each of which confirmed patient consent and participation in an Institutional Review Board (IRB) approved protocol.Sex as a biological variable not detected. Randomization not detected. Blinding not detected. Power Analysis not detected. Table 2: Resources
Antibodies Sentences Resources More detailed information about each sample and the demographics, infection/vaccination timeline, and patient outcomes can be viewed in Supplemental Tables S1-S4. Immunoassays: Anti-SARS-CoV-2 IgG antibodies were detected with an enzyme-linked immunosorbent assay (ELISA) kit (DBC anti-SARS-CoV-2 ELISA, DBC-IGG-19) with interim authorization by Health Canada. Anti-SARS-CoV-2 IgGsuggested: Noneanti-SARS-CoV-2suggested: NoneResults from OddPub: We did not detect open data. We also did not detect open code. Researchers are encouraged to share open data when possible (see Nature blog).
Results from LimitationRecognizer: We detected the following sentences addressing limitations in the study:Perhaps then, the experimental design of the DMS study is less sensitive to detecting immune evasion mutations of this type—an inconsistency that exposes limitations of DMS [32] and highlights the significance of testing the ability of immune (COVID-19 positive) sera to recognize new variants with real human samples and serological-based assays. Mutation S477N—that has emerged several times during the pandemic [31]—was found in one study to be resistant to neutralization by a panel of monoclonal antibodies, but by contrast, responds similarly to the WT when tested with convalescence (polyclonal) serum [33]—a result that aligns with the data of this study (Figure 2), once again underscoring the advantage of testing real patient sera to evaluate the antigenicity of new mutations. A recent study found lineage B.1.617.2 (Delta) to be associated with an increase in disease severity [34]. This variant also caused a higher rate of vaccine breakthrough cases (17.4% compared to 5.8% for all other variants) in Texas, with 8.4% of all COVID-19 cases occurring in fully vaccinated individuals [35]. In our study, the Delta and kappa variants (which share the L452R mutation) eluded vaccine and infection sera antibodies more than the WT in all cohorts except for critically ill patients (Figure 2). However, in vaccinated individuals, we observed a shift towards higher ODs when mutation K417N was added to the Delta variant mutations L452R and T478K to replicate the Delta Plus variant (B1.617.3...
Results from TrialIdentifier: We found the following clinical trial numbers in your paper:
Identifier Status Title ISRCTN66726260 NA NA Results from Barzooka: We did not find any issues relating to the usage of bar graphs.
Results from JetFighter: We did not find any issues relating to colormaps.
Results from rtransparent:- Thank you for including a conflict of interest statement. Authors are encouraged to include this statement when submitting to a journal.
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- No protocol registration statement was detected.
Results from scite Reference Check: We found no unreliable references.
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