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,
  • Raghu Kalluri

Journal volume & issue
Vol. 5, no. 18

Abstract

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Evaluation 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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