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      Evaluation of Commercial Anti-SARS-CoV-2 Antibody Assays and Comparison of Standardized Titers in Vaccinated Health Care Workers

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          ABSTRACT

          With the availability of vaccines, commercial assays detecting anti-severe acute respiratory syndrome coronavirus-2 antibodies (Ab) evolved toward quantitative assays directed to the spike glycoprotein or its receptor binding domain (RBD). The main objective of the present study was to compare the Ab titers obtained with quantitative commercial binding Ab assays, after one dose (convalescent individuals) or two doses (naive individuals) of vaccine, in health care workers (HCW). Antibody titers were measured in 255 sera (from 150 HCW) with five quantitative immunoassays (Abbott RBD IgG II quant, bioMérieux RBD IgG, DiaSorin Trimeric spike IgG, Siemens Healthineers RBD IgG, Wantai RBD IgG). One qualitative total antibody anti-RBD detection assay (Wantai) was used to detect previous infection before vaccination. The results are presented in binding Ab units (BAU)/mL after application, when possible, of a conversion factor provided by the manufacturers and established from a World Health Organization internal standard. There was a 100% seroconversion with all assays evaluated after two doses of vaccine. With assays allowing BAU/mL correction, Ab titers were correlated (Pearson correlation coefficient, ρ, range: 0.85–0.94). The titer differences varied by a mean of 10.6% between Siemens and bioMérieux assays to 60.9% between Abbott and DiaSorin assays. These results underline the importance of BAU conversion for the comparison of Ab titer obtained with the different quantitative assays. However, significant differences persist, notably, between kits detecting Ab against the different antigens. A true standardization of the assays would be to include the International Standard in the calibration of each assay to express the results in IU/mL.

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          Isolation of potent SARS-CoV-2 neutralizing antibodies and protection from disease in a small animal model

          Countermeasures to prevent and treat COVID-19 are a global health priority. We enrolled a cohort of SARS-CoV-2-recovered participants, developed neutralization assays to interrogate antibody responses, adapted our high-throughput antibody generation pipeline to rapidly screen over 1800 antibodies, and established an animal model to test protection. We isolated potent neutralizing antibodies (nAbs) to two epitopes on the receptor binding domain (RBD) and to distinct non-RBD epitopes on the spike (S) protein. We showed that passive transfer of a nAb provides protection against disease in high-dose SARS-CoV-2 challenge in Syrian hamsters, as revealed by maintained weight and low lung viral titers in treated animals. The study suggests a role for nAbs in prophylaxis, and potentially therapy, of COVID-19. The nAbs define protective epitopes to guide vaccine design.
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            Correlates of Protection Against SARS-CoV-2 in Rhesus Macaques

            Recent studies have reported protective efficacy of both natural immunity 1 and vaccine-induced immunity 2 – 7 against severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) challenge in rhesus macaques. However, the importance of humoral and cellular immunity for protection against SARS-CoV-2 infection remains to be determined. Here we show that adoptive transfer of purified IgG from convalescent macaques protects naïve recipient rhesus macaques against SARS-CoV-2 challenge in a dose dependent fashion. Depletion of CD8+ T cells in convalescent animals partially abrogated the protective efficacy of natural immunity against SARS-CoV-2 re-challenge, suggesting the importance of cellular immunity in the context of waning or subprotective antibody titers. These data demonstrate that relatively low antibody titers are sufficient for protection against SARS-CoV-2 in rhesus macaques, and that cellular immune responses may also contribute to protection if antibody responses are suboptimal. We also show that higher antibody titers are required for therapy of SARS-CoV-2 infection in macaques. These findings have important implications for the development of SARS-CoV-2 vaccines and immune-based therapeutics.
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              Neutralizing Antibodies Correlate with Protection from SARS-CoV-2 in Humans during a Fishery Vessel Outbreak with a High Attack Rate

              The development of vaccines against SARS-CoV-2 would be greatly facilitated by the identification of immunological correlates of protection in humans. However, to date, studies on protective immunity have been performed only in animal models and correlates of protection have not been established in humans. Here, we describe an outbreak of SARS-CoV-2 on a fishing vessel associated with a high attack rate. Predeparture serological and viral reverse transcription-PCR (RT-PCR) testing along with repeat testing after return to shore was available for 120 of the 122 persons on board over a median follow-up of 32.
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                Author and article information

                Contributors
                Role: Editor
                Journal
                J Clin Microbiol
                J Clin Microbiol
                JCM
                Journal of Clinical Microbiology
                American Society for Microbiology (1752 N St., N.W., Washington, DC )
                0095-1137
                1098-660X
                27 October 2021
                19 January 2022
                January 2022
                19 January 2022
                : 60
                : 1
                : e01746-21
                Affiliations
                [a ] Laboratoire de Virologie, Institut des Agents Infectieux, Laboratoire associé au Centre National de Référence des virus des infections respiratoires, Hospices Civils de Lyongrid.413852.9, , IAI, Centre de Biologie Nord, Groupement Hospitalier Nord, Lyon, France
                [b ] Occupational Health and Medicine Department, Hospices Civils de Lyongrid.413852.9, , Lyon, France
                [c ] Laboratory of Immunology and Immunomonitoring, CIC 1408 INSERM, GIMAP EA3064, University Hospital of Saint-Etienne, Saint-Etienne, France
                [d ] CIRI-International Center of Research in Infectiology, INSERM U1111, CNRS UMR5308, ENS Lyon, Claude Bernard Lyon 1 University, Lyon, France
                [e ] CNRS, UMR 5558, University of Lyon, Laboratoire de Biométrie et Biologie Evolutive, Equipe Biostatistique-Santé, Villeurbanne, France
                [f ] Immunology Department, Lyon Sud Hospital, Hospices Civils de Lyongrid.413852.9, , Pierre-Bénite Cedex, France
                Mayo Clinic
                Author notes

                Citation Saker K, Escuret V, Pitiot V, Massardier-Pilonchéry A, Paul S, Mokdad B, Langlois-Jacques C, Rabilloud M, Goncalves D, Fabien N, Guibert N, Fassier J-B, Bal A, Trouillet-Assant S, Trabaud M-A. 2022. Evaluation of commercial anti-SARS-CoV-2 antibody assays and comparison of standardized titers in vaccinated health care workers. J Clin Microbiol 60:e01746-21. https://doi.org/10.1128/JCM.01746-21.

                Author information
                https://orcid.org/0000-0002-5298-1002
                https://orcid.org/0000-0002-8830-4273
                https://orcid.org/0000-0002-0261-2495
                https://orcid.org/0000-0001-8614-1071
                Article
                01746-21 jcm.01746-21
                10.1128/JCM.01746-21
                8769743
                34705539
                8c9bea5d-a37d-439a-953f-efab58906131
                Copyright © 2022 American Society for Microbiology.

                All Rights Reserved.

                This article is made available via the PMC Open Access Subset for unrestricted noncommercial re-use and secondary analysis in any form or by any means with acknowledgement of the original source. These permissions are granted for the duration of the World Health Organization (WHO) declaration of COVID-19 as a global pandemic.

                History
                : 11 August 2021
                : 2 September 2021
                : 18 October 2021
                Page count
                Figures: 3, Tables: 2, Equations: 0, References: 16, Pages: 8, Words: 4430
                Funding
                Funded by: Hospices Civils de Lyon (HCL), FundRef https://doi.org/10.13039/501100006451;
                Award Recipient : Award Recipient : Award Recipient : Award Recipient : Award Recipient : Award Recipient : Award Recipient : Award Recipient : Award Recipient : Award Recipient : Award Recipient : Award Recipient : Award Recipient : Award Recipient : Award Recipient :
                Categories
                Virology
                virology, Virology
                Custom metadata
                January 2022
                free

                Microbiology & Virology
                sars-cov-2 antibodies,quantification,commercial assays,standardized titers,vaccination,health care workers,immunization

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