tetano
Editor, Senior Moderator
JCI Insight
. 2020 Aug 14;142386.
doi: 10.1172/jci.insight.142386. Online ahead of print.
Heterogeneous antibodies against SARS-CoV-2 spike receptor binding domain and nucleocapsid with implications on COVID-19 immunity
Kathleen M McAndrews[SUP] 1 [/SUP], Dara P Dowlatshahi[SUP] 1 [/SUP], Jianli Dai[SUP] 1 [/SUP], Lisa M Becker[SUP] 1 [/SUP], Janine Hensel[SUP] 1 [/SUP], Laura M Snowden[SUP] 1 [/SUP], Jennifer M Leveille[SUP] 1 [/SUP], Michael R Brunner[SUP] 2 [/SUP], Kylie Holden[SUP] 2 [/SUP], Nikolas S Hopkins[SUP] 2 [/SUP], Alexandria Harris[SUP] 2 [/SUP], Jerusha J Kumpati[SUP] 2 [/SUP], Michael A Whitt[SUP] 2 [/SUP], J Jack Lee[SUP] 3 [/SUP], Luis Ostrosky-Zeichner[SUP] 4 [/SUP], Ramesha Papanna[SUP] 5 [/SUP], Valerie LeBleu[SUP] 1 [/SUP], James Allison[SUP] 6 [/SUP], Raghu Kalluri[SUP] 1 [/SUP]
Affiliations
Abstract
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 to 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 enzyme-linked immunosorbent assay (ELISA) using recombinant S-RBD and N-protein for the detection of circulating antibodies in 138 serial serum samples from 30 RT-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 to the two different viral proteins showed a moderate correlation. Antibodies to N-protein were detected at a rate of 3.6% in healthy and non-COVID-19 sera collected during the pandemic in 2020, whereas 1.6% 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 cautions against the extensive use of N-protein based serology testing for determination of potential COVID-19 immunity.
Keywords: Adaptive immunity; COVID-19; Immunology.
. 2020 Aug 14;142386.
doi: 10.1172/jci.insight.142386. Online ahead of print.
Heterogeneous antibodies against SARS-CoV-2 spike receptor binding domain and nucleocapsid with implications on COVID-19 immunity
Kathleen M McAndrews[SUP] 1 [/SUP], Dara P Dowlatshahi[SUP] 1 [/SUP], Jianli Dai[SUP] 1 [/SUP], Lisa M Becker[SUP] 1 [/SUP], Janine Hensel[SUP] 1 [/SUP], Laura M Snowden[SUP] 1 [/SUP], Jennifer M Leveille[SUP] 1 [/SUP], Michael R Brunner[SUP] 2 [/SUP], Kylie Holden[SUP] 2 [/SUP], Nikolas S Hopkins[SUP] 2 [/SUP], Alexandria Harris[SUP] 2 [/SUP], Jerusha J Kumpati[SUP] 2 [/SUP], Michael A Whitt[SUP] 2 [/SUP], J Jack Lee[SUP] 3 [/SUP], Luis Ostrosky-Zeichner[SUP] 4 [/SUP], Ramesha Papanna[SUP] 5 [/SUP], Valerie LeBleu[SUP] 1 [/SUP], James Allison[SUP] 6 [/SUP], Raghu Kalluri[SUP] 1 [/SUP]
Affiliations
- PMID: 32796155
- DOI: 10.1172/jci.insight.142386
Abstract
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 to 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 enzyme-linked immunosorbent assay (ELISA) using recombinant S-RBD and N-protein for the detection of circulating antibodies in 138 serial serum samples from 30 RT-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 to the two different viral proteins showed a moderate correlation. Antibodies to N-protein were detected at a rate of 3.6% in healthy and non-COVID-19 sera collected during the pandemic in 2020, whereas 1.6% 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 cautions against the extensive use of N-protein based serology testing for determination of potential COVID-19 immunity.
Keywords: Adaptive immunity; COVID-19; Immunology.