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Anti-SARS-CoV-2 antibody levels are concordant across multiple platforms but are not fully
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predictive of sterilizing immunity
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Benjamin T. Bradley
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, Andrew Bryan
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, Susan L. Fink
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, Erin A. Goecker
1
, Pavitra Roychoudhury
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,
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Meei-Li Huang
1
, Haiying Zhu
1
, Anu Chaudhary
1
, Bhanupriya Madarampalli
1
, Joyce Y.C. Lu
1
, Kathy
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Strand
2
, Estella Whimbey
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, Chloe Bryson-Cahn
2
, Adrienne Schippers
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, Nandita S. Mani
2
, Gregory
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Pepper
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, Keith R. Jerome
1,3
, Chihiro Morishima
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, Robert W. Coombs
1,2
, Mark Wener
1
, Seth
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Cohen
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, Alexander L. Greninger
1,3 #
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1
Department of Laboratory Medicine and Pathology, University of Washington Medical Center,
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Seattle, WA
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Division of Infectious Diseases, Department of Medicine, University of Washington Medical
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Center, Seattle, WA
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Vaccine and Infectious Disease Division, Fred Hutchinson Cancer Research Center, Seattle, WA
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15
#
Corresponding author
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Alexander L. Greninger, agrening@uw.edu
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1616 Eastlake Ave E, Suite 320, Seattle, WA 98102
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Phone: 415 439 3448, Fax: 206 616 4340
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Running Title: anti-S assays
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Keywords: Abbott Architect, SARS-CoV-2, spike protein, spike IgG, serology, COVID-19,
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coronavirus
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. CC-BY 4.0 International licenseIt is made available under a
is the author/funder, who has granted medRxiv a license to display the preprint in perpetuity. (which was not certified by peer review)
The copyright holder for this preprint this version posted April 29, 2021. ; https://doi.org/10.1101/2021.04.26.21256118doi: medRxiv preprint
NOTE: This preprint reports new research that has not been certified by peer review and should not be used to guide clinical practice.
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Abstract
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With the availability of widespread SARS-CoV-2 vaccination, high-throughput quantitative anti-
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spike serological testing will likely become increasingly important. Here, we investigated the
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performance characteristics of the recently FDA authorized semi-quantitative anti-spike
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AdviseDx SARS-CoV-2 IgG II assay compared to the FDA authorized anti-nucleocapsid Abbott
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Architect SARS-CoV-2 IgG, Roche elecsys Anti-SARS-CoV-2-S, EuroImmun Anti-SARS-CoV-2
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ELISA, and GenScript surrogate virus neutralization assays and examined the humoral response
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associated with vaccination, natural protection, and breakthrough infection. The AdviseDx
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assay had a clinical sensitivity at 14 days post-symptom onset or 10 days post PCR detection of
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95.6% (65/68, 95% CI: 87.8-98.8%) with two discrepant individuals seroconverting shortly
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thereafter. The AdviseDx assay demonstrated 100% positive percent agreement with the four
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other assays examined using the same symptom onset or PCR detection cutoffs. Using a
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recently available WHO International Standard for anti-SARS-CoV-2 antibody, we provide assay
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unit conversion factors to international units for each of the assays examined. We performed a
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longitudinal survey of healthy vaccinated individuals, finding median AdviseDx immunoglobulin
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levels peaked seven weeks post-first vaccine dose at approximately 4,000 IU/mL. Intriguingly,
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among the five assays examined, there was no significant difference in antigen binding level or
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neutralizing activity between two seropositive patients protected against SARS-CoV-2 infection
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in a previously described fishing vessel outbreak and five healthcare workers who experienced
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vaccine breakthrough of SARS-CoV-2 infection – all with variants of concern. These findings
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suggest that protection against SARS-CoV-2 infection cannot currently be predicted exclusively
43
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is the author/funder, who has granted medRxiv a license to display the preprint in perpetuity. (which was not certified by peer review)
The copyright holder for this preprint this version posted April 29, 2021. ; https://doi.org/10.1101/2021.04.26.21256118doi: medRxiv preprint
3
using
in vitro
antibody assays against wildtype SARS-CoV-2 spike. Further work is required to
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establish protective corre lates of protection for SARS-CoV-2 infection.
45
. CC-BY 4.0 International licenseIt is made available under a
is the author/funder, who has granted medRxiv a license to display the preprint in perpetuity. (which was not certified by peer review)
The copyright holder for this preprint this version posted April 29, 2021. ; https://doi.org/10.1101/2021.04.26.21256118doi: medRxiv preprint
4
Introduction
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Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) the etiologic agent of
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coronavirus disease 19 (COVID-19) is responsible for an ongoing global pandemic. In addition to
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infection control measures such as social distancing and masking, controlling the spread of the
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outbreak will require a global vaccination campaign. Currently, three vaccines have received
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FDA emergency use authorization with other candidates in late-phase clinical trials (1).
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Common to all vaccine candidates is the inclusion of the receptor binding domain (RBD) or full-
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length spike (S) of SARS-CoV-2 (2).
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For SARS-CoV-2 and related coronaviruses, antibodies to the RBD of the spike protein have
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demonstrated potent neutralizing activity at nanomolar concentrations (3, 4). In a recent meta-
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analysis of individuals with naturally-acquired SARS-CoV-2 infection, neutralizing antibodies
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were first detectable between seven to 15 days following symptom onset (5). Despite questions
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regarding the durability of the antibody response and documented cases of reinfection,
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longitudinal analysis of IgG levels and neutralizing potency suggest immunity persists in most
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individuals for as long a time period as has been examinable to date (6, 7). However, some
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individuals, including those who are older or immunosuppressed, may be at risk for a
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suboptimal response to vaccination (8, 9).
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The presence of neutralizing antibodies due to prior infection or vaccination has been shown to
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be a correlate of protection against SARS-CoV-2 infection (10–12). Although Phase III vaccine
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trials demonstrated excellent efficacies among treated populations (13, 14), a number of
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. CC-BY 4.0 International licenseIt is made available under a
is the author/funder, who has granted medRxiv a license to display the preprint in perpetuity. (which was not certified by peer review)
The copyright holder for this preprint this version posted April 29, 2021. ; https://doi.org/10.1101/2021.04.26.21256118doi: medRxiv preprint
5
subpopulations including pregnant women and immunocompromised individuals were
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excluded from these trials. Moreover, uncertainty exists over the durability of protection after
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vaccination (15). High-throughput, widely available laboratory measurements of protective
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correlates would be extremely helpful in these and other populations. The current gold-
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standard test, known as the plaque reduction neutralization assay (PRNA), is resource intensive
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and requires BSL-3 conditions for testing. Currently, one surrogate neutralization assay has
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received EUA-approval for clinical use. While this assay can be performed in BSL-2 laboratories
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and has shown excellent correlation to PRNAs, it also suffers from similar limitations of
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throughput and cost (16). The most widely used clinical platforms for monitoring immunity to
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vaccine-preventable diseases including hepatitis B virus, measles virus, and varicella-zoster
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virus are high-throughput, low-cost immunoassay analyzers, including the Roche cobas, Abbott
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Architect, and Diasorin XL platforms, among others. Recently, the Abbott AdviseDx SARS-CoV-2
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IgG II assay received emergency use authorization by the FDA. This chemiluminescent
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microparticle immunoassay (CIMA) for the Abbott Architect platform is designed for semi-
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quantitative detection of IgG class antibodies to the RBD of the SARS-CoV-2 spike protein.
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Our laboratory previously examined the clinical performance characteristics of the anti-N SARS-
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CoV-2 IgG assay for the Abbott Architect and found it to have adequate performance for
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determining prior SARS-CoV-2 infection in a hospitalized cohort (17). However, this assay is
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qualitative and designed to detect antibodies to the nucleocapsid, precluding the ability to
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monitor vaccine response. In this study we examine the performance of the AdviseDx SARS-
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CoV-2 IgG II assay and correlate its performance to four other assays (Abbott Architect SARS-
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. CC-BY 4.0 International licenseIt is made available under a
is the author/funder, who has granted medRxiv a license to display the preprint in perpetuity. (which was not certified by peer review)
The copyright holder for this preprint this version posted April 29, 2021. ; https://doi.org/10.1101/2021.04.26.21256118doi: medRxiv preprint