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J Clin Microbiol . SARS-CoV-2 assays to detect functional antibody responses that block ACE2 recognition in vaccinated animals and infected patient

tetano

Editor, Senior Moderator
J Clin Microbiol


. 2020 Aug 27;JCM.01533-20.
doi: 10.1128/JCM.01533-20. Online ahead of print.
SARS-CoV-2 assays to detect functional antibody responses that block ACE2 recognition in vaccinated animals and infected patients


Susanne N Walker[SUP] 1 [/SUP], Neethu Chokkalingam[SUP] 1 [/SUP], Emma L Reuschel[SUP] 1 [/SUP], Mansi Purwar[SUP] 1 [/SUP], Ziyang Xu[SUP] 1 [/SUP], Ebony N Gary[SUP] 1 [/SUP], Kevin Y Kim[SUP] 1 [/SUP], Michaela Helble[SUP] 1 [/SUP], Katherine Schultheis[SUP] 2 [/SUP], Jewell Walters[SUP] 2 [/SUP], Stephanie Ramos[SUP] 2 [/SUP], Kar Muthumani[SUP] 1 [/SUP], Trevor R F Smith[SUP] 2 [/SUP], Kate E Broderick[SUP] 2 [/SUP], Pablo Tebas[SUP] 3 [/SUP], Ami Patel[SUP] 1 [/SUP], David B Weiner[SUP] 1 [/SUP], Daniel W Kulp[SUP] 4 5 [/SUP]



Affiliations

Abstract

SARS-CoV-2 (Severe Acute Respiratory Syndrome Coronavirus 2) has caused a global pandemic of COVID-19 resulting in cases of mild to severe respiratory distress and significant mortality. The global outbreak of this novel coronavirus has now infected >20 million people worldwide with >5 million cases in the US (August 11[SUP]th[/SUP], 2020). The development of diagnostic and research tools to determine infection and vaccine efficacy are critically needed. We have developed multiple serologic assays using newly designed SARS-CoV-2 reagents for detecting the presence of receptor-binding antibodies in sera. The first assay is SPR-based and can quantitate both antibody binding to the SARS-CoV-2 spike protein and blocking to the Angiotensin-converting enzyme 2 (ACE2) receptor in a single experiment. The second assay is ELISA-based and can measure competition and blocking of the ACE2 receptor to the SARS-CoV-2 spike protein with anti-spike antibodies. The assay is highly versatile, and we demonstrate the broad utility of the assay by measuring antibody functionality of sera from small animals and non-human primates immunized with an experimental SARS-CoV-2 vaccine. In addition, we employ the assay to measure receptor-blocking of sera from SARS-CoV-2 infected patients. The assay is shown to correlate with pseudovirus neutralization titers. This type of rapid, surrogate neutralization diagnostic can be employed widely to help study SARS-CoV-2 infection and for assessing efficacy of vaccines.
 
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