TY - JOUR T1 - Heterogeneous antibodies against SARS-CoV-2 spike receptor binding domain and nucleocapsid with implications for COVID-19 immunity. AU - McAndrews,Kathleen M, AU - Dowlatshahi,Dara P, AU - Dai,Jianli, AU - Becker,Lisa M, AU - Hensel,Janine, AU - Snowden,Laura M, AU - Leveille,Jennifer M, AU - Brunner,Michael R, AU - Holden,Kylie W, AU - Hopkins,Nikolas S, AU - Harris,Alexandria M, AU - Kumpati,Jerusha, AU - Whitt,Michael A, AU - Lee,J Jack, AU - Ostrosky-Zeichner,Luis L, AU - Papanna,Ramesha, AU - LeBleu,Valerie S, AU - Allison,James P, AU - Kalluri,Raghu, Y1 - 2020/09/17/ PY - 2020/07/17/received PY - 2020/08/13/accepted PY - 2020/8/17/pubmed PY - 2020/9/30/medline PY - 2020/8/16/entrez KW - Adaptive immunity KW - COVID-19 KW - Immunology JF - JCI insight JO - JCI Insight VL - 5 IS - 18 N2 - 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. SN - 2379-3708 UR - https://www.unboundmedicine.com/medline/citation/32796155/Heterogeneous_antibodies_against_SARS_CoV_2_spike_receptor_binding_domain_and_nucleocapsid_with_implications_for_COVID_19_immunity_ L2 - https://doi.org/10.1172/jci.insight.142386 DB - PRIME DP - Unbound Medicine ER -