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An Assessment of Serological Assays for SARS-CoV-2 as Surrogates for Authentic Virus Neutralization.
Wohlgemuth, Nicholas; Whitt, Kendall; Cherry, Sean; Kirkpatrick Roubidoux, Ericka; Lin, Chun-Yang; Allison, Kim J; Gowen, Ashleigh; Freiden, Pamela; Allen, E Kaitlynn; Gaur, Aditya H; Estepp, Jeremie H; Tang, Li; Mori, Tomi; Hijano, Diego R; Hakim, Hana; McGargill, Maureen A; Krammer, Florian; Whitt, Michael A; Wolf, Joshua; Thomas, Paul G; Schultz-Cherry, Stacey.
  • Wohlgemuth N; Department of Infectious Diseases, St. Jude Children's Research Hospital, Memphis, Tennessee, USA.
  • Whitt K; Department of Microbiology, Immunology and Biochemistry, University of Tennessee Health Science Centergrid.267301.1, Memphis, Tennessee, USA.
  • Cherry S; Department of Infectious Diseases, St. Jude Children's Research Hospital, Memphis, Tennessee, USA.
  • Kirkpatrick Roubidoux E; Department of Infectious Diseases, St. Jude Children's Research Hospital, Memphis, Tennessee, USA.
  • Lin CY; Department of Immunology, St. Jude Children's Research Hospital, Memphis, Tennessee, USA.
  • Allison KJ; Department of Infectious Diseases, St. Jude Children's Research Hospital, Memphis, Tennessee, USA.
  • Gowen A; Department of Infectious Diseases, St. Jude Children's Research Hospital, Memphis, Tennessee, USA.
  • Freiden P; Department of Infectious Diseases, St. Jude Children's Research Hospital, Memphis, Tennessee, USA.
  • Allen EK; Department of Immunology, St. Jude Children's Research Hospital, Memphis, Tennessee, USA.
  • Gaur AH; Department of Infectious Diseases, St. Jude Children's Research Hospital, Memphis, Tennessee, USA.
  • Estepp JH; Department of Hematology, St. Jude Children's Research Hospital, Memphis, Tennessee, USA.
  • Tang L; Department of Global Pediatric Medicine, St. Jude Children's Research Hospital, Memphis, Tennessee, USA.
  • Mori T; Department of Biostatistics, St. Jude Children's Research Hospital, Memphis, Tennessee, USA.
  • Hijano DR; Department of Biostatistics, St. Jude Children's Research Hospital, Memphis, Tennessee, USA.
  • Hakim H; Department of Infectious Diseases, St. Jude Children's Research Hospital, Memphis, Tennessee, USA.
  • McGargill MA; Department of Infectious Diseases, St. Jude Children's Research Hospital, Memphis, Tennessee, USA.
  • Krammer F; Department of Immunology, St. Jude Children's Research Hospital, Memphis, Tennessee, USA.
  • Whitt MA; Department of Microbiology, Icahn School of Medicine at Mount Sinai, New York, New York, USA.
  • Wolf J; Department of Microbiology, Immunology and Biochemistry, University of Tennessee Health Science Centergrid.267301.1, Memphis, Tennessee, USA.
  • Thomas PG; Department of Infectious Diseases, St. Jude Children's Research Hospital, Memphis, Tennessee, USA.
  • Schultz-Cherry S; Department of Immunology, St. Jude Children's Research Hospital, Memphis, Tennessee, USA.
Microbiol Spectr ; 9(2): e0105921, 2021 10 31.
Article in English | MEDLINE | ID: covidwho-1495012
ABSTRACT
Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) emerged in late 2019 and has since caused a global pandemic resulting in millions of cases and deaths. Diagnostic tools and serological assays are critical for controlling the outbreak, especially assays designed to quantitate neutralizing antibody levels, considered the best correlate of protection. As vaccines become increasingly available, it is important to identify reliable methods for measuring neutralizing antibody responses that correlate with authentic virus neutralization but can be performed outside biosafety level 3 (BSL3) laboratories. While many neutralizing assays using pseudotyped virus have been developed, there have been few studies comparing the different assays to each other as surrogates for authentic virus neutralization. Here, we characterized three enzyme-linked immunosorbent assays (ELISAs) and three pseudotyped vesicular stomatitis virus (VSV) neutralization assays and assessed their concordance with authentic virus neutralization. The most accurate assays for predicting authentic virus neutralization were luciferase- and secreted embryonic alkaline phosphatase (SEAP)-expressing pseudotyped virus neutralizations, followed by green fluorescent protein (GFP)-expressing pseudotyped virus neutralization, and then the ELISAs. IMPORTANCE The ongoing COVID-19 pandemic is caused by infection with severe acute respiratory syndrome virus 2 (SARS-CoV-2). Prior infection or vaccination can be detected by the presence of antibodies in the blood. Antibodies in the blood are also considered to be protective against future infections from the same virus. The "gold standard" assay for detecting protective antibodies against SARS-CoV-2 is neutralization of authentic SARS-CoV-2 virus. However, this assay can only be performed under highly restrictive biocontainment conditions. We therefore characterized six antibody-detecting assays for their correlation with authentic virus neutralization. The significance of our research is in outlining the advantages and disadvantages of the different assays and identifying the optimal surrogate assay for authentic virus neutralization. This will allow for more accurate assessments of protective immunity against SARS-CoV-2 following infection and vaccination.
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Full text: Available Collection: International databases Database: MEDLINE Document Type: Article Main subject: Neutralization Tests / Antibodies, Neutralizing / COVID-19 Serological Testing / SARS-CoV-2 / COVID-19 / Antibodies, Viral Subject: Neutralization Tests / Antibodies, Neutralizing / COVID-19 Serological Testing / SARS-CoV-2 / COVID-19 / Antibodies, Viral Type of study: Prognostic study Language: English Journal: Microbiol Spectr Clinical aspect: Diagnosis / Prediction / Prognosis Year: 2021

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Full text: Available Collection: International databases Database: MEDLINE Document Type: Article Main subject: Neutralization Tests / Antibodies, Neutralizing / COVID-19 Serological Testing / SARS-CoV-2 / COVID-19 / Antibodies, Viral Subject: Neutralization Tests / Antibodies, Neutralizing / COVID-19 Serological Testing / SARS-CoV-2 / COVID-19 / Antibodies, Viral Type of study: Prognostic study Language: English Journal: Microbiol Spectr Clinical aspect: Diagnosis / Prediction / Prognosis Year: 2021
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