Dogne, Jean-Michel

Douxfils, Jonathan

FAVRESSE, Julien

Gillot, Constant

Maloteau, Vincent

English

Repository of the University of Namur

RESEARCH OUTPUTS / RÉSULTATS DE RECHERCHEAuthor(s) - Auteur(s) :Publication date - Date de publication :Permanent link - Permalien :Rights / License - Licence de droit d’auteur :Bibliothèque Universitaire Moretus PlantinInstitutional Repository - Research PortalDépôt Institutionnel - Portail de la Rechercheresearchportal.unamur.beUniversity of NamurDynamics of Neutralizing Antibody Responses Following Natural SARS-CoV-2Infection and Correlation with Commercial Serologic Tests. A reappraisal and IndirectComparison With Vaccinated SubjectsGillot, Constant; FAVRESSE, Julien; Maloteau, Vincent; Dogne, Jean-Michel; Douxfils,JonathanPublication date:2023Document VersionPeer reviewed versionLink to publicationCitation for pulished version (HARVARD):Gillot, C, FAVRESSE, J, Maloteau, V, Dogne, J-M & Douxfils, J 2023, 'Dynamics of Neutralizing AntibodyResponses Following Natural SARS-CoV-2 Infection and Correlation with Commercial Serologic Tests. Areappraisal and Indirect Comparison With Vaccinated Subjects'.General rightsCopyright and moral rights for the publications made accessible in the public portal are retained by the authors and/or other copyright ownersand it is a condition of accessing publications that users recognise and abide by the legal requirements associated with these rights.            • Users may download and print one copy of any publication from the public portal for the purpose of private study or research.            • You may not further distribute the material or use it for any profit-making activity or commercial gain            • You may freely distribute the URL identifying the publication in the public portal ?Take down policyIf you believe that this document breaches copyright please contact us providing details, and we will remove access to the work immediatelyand investigate your claim.Download date: 25. Apr. 2023Dynamics of Neutralizing Antibody Responses Following Natural SARS-CoV-2 Infection and Correlation with Commercial SerologicTests. A reappraisal and Indirect Comparison With Vaccinated SubjectsConstant Gillot1, Julien Favresse1,2, Vincent Maloteau1, Jean-Michel Dogné1 and Jonathan Douxfils1,31Department of Pharmacy, Namur Research Institute for Life Sciences, University of Namur, 5000 Namur, Belgium2Department of Laboratory Medicine, Clinique St-Luc Bouge, 5000 Namur, Belgium3Qualiblood s.a., 5000 Namur, BelgiumINTRODUCTIONFollowing COVID-19 infection or vaccination, numerousantibodies are produced targeting different epitopes ofthe virus or the spike protein. Nevertheless, not all theseantibodies are able to efficiently neutralize the virussince they can bind an epitope which is not essential forthe virus entry into the cell. Therefore, the detection ofneutralizing antibodies (NAbs) is of particularimportance because these are the antibodies that canprevent the binding of the RBD of the S protein to theangiotensin-converting enzyme 2 (ACE2) receptorpresent at the surface of human cells, preventing theentry of the virus into the host cells.METHODIn this cohort, we assessed:Ø Six commercial binding assays:Ø Roche nucleocapsid (NCP) total antibodyassayØ Roche RBD total antibody assayØ DiaSorin S1/S2 IgG assayØ Ortho S1 IgG assayØ Ortho S1 total antibody assayØ Phadia S1 IgG assayØ Two neutralizing techniques:Ø Surrogate virus neutralization test(sVNT)Ø Pseudo virus neutralization test(pVNT)Study Population:Ø 62 RT-PCR confirmed COVID-19 patients for 114 samples from day 1 to day 296 aftersymptoms onset.CONTACT INFORMATIONConstant GillotConstant.gillot@unamur.be+ 32 (0)81 72 42 92RESULTSCONCLUSION30 90 150 210 270Day 18011/201/101/1001/10001/10 000Non-HospitalizationHospitalization30 90 150 210 270Day 18011/101/1001/10001/10 0001/20SeropositiveSeronegativeDays post symptoms onsetpVNT titer dilutionA BConcerning COVID-19 patients, from day 14 to day 291, more than 75% of the samples were positive forNAbs (n=87/110, 79.1%). Six months post symptoms onset, the majority of the samples (n=44/52,84.6%) were still positive for NAbs. (Figure 2 A)This is in sharp contrast with the results we obtained 6 months post-vaccination in our cohort ofhealthcare workers which have received the two dose regimens of BNT162b2. In this cohort 43%(n=25/58) of the participants no longer exhibit NAbs activity 180 days after the administration of thefirst dose of BNT162b2.Those who were seropositive at baseline seemed to lose their neutralizing capacity (n=7/18, 39%).(Figure 2 B)0.0 0.5 1.00.00.51.01 - SpecificitySensitivityPhadia S1 IgG | AUC: 0.570 (95% CI: 0.425 - 0.715)Ortho S1 total Ab | AUC: 0.748 (95% CI: 0.646 - 0.851)Ortho S1 IgG | AUC: 0.653 (95% CI: 0.522 - 0.783)Diasorin S1+ S2 IgG | AUC: 0.675 (95% CI: 0.550 - 0.800)Roche NCP total Ab | AUC: 0.806 (95% CI: 0.719 - 0.894)sVNT NAbs | AUC: 0.944 (95% CI: 0.894 - 0.994)Serological assayRoche RBD total antibody assayRoche NCP total antibody assayDiaSorin S1/S2 IgG assay Ortho S1 IgG assayOrtho S1 total antibody assayPhadia S1 IgG assay sVNTCut-off definitionManufacturer:0.8 U/mL Manufacturer:1.0 COI Manufacturer:15.0 U/mL Manufacturer:1.0 S/V Manufacturer:1.0 S/V Manufacturer:0.7 U/mL Manufacturer:10.0 U/mL Adapted:5.9 U/mLAdapted:37.7 COIAdapted:11.4 U/mLAdapted:0.3 S/VAdapted:165.0 S/VAdapted:2.5 U/mLAdapted:16.6 U/mLSensitivity(95% CI)97.8%(92.2%-99.7%)97.8%(92.2%-99.7%)87.6% (79.0% - 93.7%)90.0%(81.9-95.3%)98.9%(94.0%-100.0%)97.1% (92.1% - 99.7%)97.8%(92.3% - 99.7%)88.8%(80.3% - 94.5%)61.8%(50.9% - 71.9%)91.0% (83.1% - 96.0%)93.3%(85.9% - 97.5%)53.9%(43.0% - 64.6%)96.6%(90.5% - 99.3%)97.7%(92.1% - 99.7%)Specificity(95% CI)33.3%(15.6-55.3%)12.5%(2.7%-32.4%)44.0%(24.4% - 65.1%)41.7%(22.1%-63.4%)16.7%(4.7%-37.4%)16.0%(4.5% - 36.1%)65.2%(42.7% - 83.6%)52.0% (31.3% - 72.2%)84.0%(63.9% - 95.5%)40.0%(21.1% - 61.3%)40.0%(21.1% - 61.3%)84.0%(63.9% - 95.5%)28.0%(12.1% - 49.4%)92.0%(74.0% - 99.0%)Using the cut-off provided by the manufacturers, the sensitivity did not statistically differbetween the different serological assays investigated in this study (Table 1, Figure 1). Thespecificity was below 50.0% for all assays meaning that these assays generate many falsepositive results for the detection of NAbs. In general, serological assays targeting totalantibodies generate less false negative results. This means that also measuring both IgA andIgM permit to better evaluate the neutralizing capacity of the serum than just targeting IgG.The sVNT test showed the best correlation with the pVNT technique.Figure 1 Table 1Figure 2The correlation between the pVNT resultsand the sVNT results is better than the othertests but the data remains veryheterogeneous. Results obtained with theinfected and the vaccinated cohort suggestthat there is a relationship between thedevelopment of NAbs and the time ofexposure to the virus. Patients withprolonged exposure to SARS-CoV-2 had ahigher NAbs titer than patients who clearedthe virus earlier. These results deservefurther investigations to better understandthe difference in the dynamic of antibodyproduction after COVID-19 disease andvaccination.

Dynamics of Neutralizing Antibody Responses Following Natural SARS-CoV-2 Infection and Correlation with Commercial Serologic Tests. A reappraisal and Indirect Comparison With Vaccinated Subjects

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Dynamics of Neutralizing Antibody Responses Following Natural SARS-CoV-2 Infection and Correlation with Commercial Serologic Tests. A reappraisal and Indirect Comparison With Vaccinated Subjects

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