• JCI insight · Sep 2020

    Heterogeneous antibodies against SARS-CoV-2 spike receptor binding domain and nucleocapsid with implications for COVID-19 immunity.

    • Kathleen M McAndrews, Dara P Dowlatshahi, Jianli Dai, Lisa M Becker, Janine Hensel, Laura M Snowden, Jennifer M Leveille, Michael R Brunner, Kylie W Holden, Nikolas S Hopkins, Alexandria M Harris, Jerusha Kumpati, Michael A Whitt, J Jack Lee, Luis L Ostrosky-Zeichner, Ramesha Papanna, Valerie S LeBleu, James P Allison, and Raghu Kalluri.
    • Metastasis Research Center, Department of Cancer Biology, University of Texas MD Anderson Cancer Center, Houston, Texas, USA.
    • JCI Insight. 2020 Sep 17; 5 (18).

    AbstractEvaluation of potential immunity against the novel severe acute respiratory syndrome (SARS) coronavirus that emerged in 2019 (SARS-CoV-2) is essential for health, as well as social and economic recovery. Generation of antibody response to SARS-CoV-2 (seroconversion) may inform on acquired immunity from prior exposure, and antibodies against the SARS-CoV-2 spike protein receptor binding domain (S-RBD) are speculated to neutralize virus infection. Some serology assays rely solely on SARS-CoV-2 nucleocapsid protein (N-protein) as the antibody detection antigen; however, whether such immune responses correlate with S-RBD response and COVID-19 immunity remains unknown. Here, we generated a quantitative serological ELISA using recombinant S-RBD and N-protein for the detection of circulating antibodies in 138 serial serum samples from 30 reverse transcription PCR-confirmed, SARS-CoV-2-hospitalized patients, as well as 464 healthy and non-COVID-19 serum samples that were collected between June 2017 and June 2020. Quantitative detection of IgG antibodies against the 2 different viral proteins showed a moderate correlation. Antibodies against N-protein were detected at a rate of 3.6% in healthy and non-COVID-19 sera collected during the pandemic in 2020, whereas 1.9% of these sera were positive for S-RBD. Approximately 86% of individuals positive for S-RBD-binding antibodies exhibited neutralizing capacity, but only 74% of N-protein-positive individuals exhibited neutralizing capacity. Collectively, our studies show that detection of N-protein-binding antibodies does not always correlate with presence of S-RBD-neutralizing antibodies and caution against the extensive use of N-protein-based serology testing for determination of potential COVID-19 immunity.

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