Heterogeneous antibodies against SARS-CoV-2 spike receptor binding domain and nucleocapsid with implications for COVID-19 immunity.
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.
['McAndrews|Kathleen M|KM|', 'Dowlatshahi|Dara P|DP|', 'Dai|Jianli|J|', 'Becker|Lisa M|LM|', 'Hensel|Janine|J|', 'Snowden|Laura M|LM|', 'Leveille|Jennifer M|JM|', 'Brunner|Michael R|MR|', 'Holden|Kylie W|KW|', 'Hopkins|Nikolas S|NS|', 'Harris|Alexandria M|AM|', 'Kumpati|Jerusha|J|', 'Whitt|Michael A|MA|', 'Lee|J Jack|JJ|', 'Ostrosky-Zeichner|Luis L|LL|', 'Papanna|Ramesha|R|', 'LeBleu|Valerie S|VS|', 'Allison|James P|JP|', 'Kalluri|Raghu|R|']
D056704:Adaptive Immunity D057134:Antibodies, Neutralizing D000914:Antibodies, Viral D000073640:Betacoronavirus D000086382:COVID-19 D000086742:COVID-19 Testing D019411:Clinical Laboratory Techniques D018352:Coronavirus Infections D005260:Female D006801:Humans D008297:Male D008875:Middle Aged D019251:Nucleocapsid D017063:Outcome Assessment, Health Care D058873:Pandemics D011024:Pneumonia, Viral D011485:Protein Binding D000086402:SARS-CoV-2 D012680:Sensitivity and Specificity D000069078:Seroconversion D012698:Serologic Tests D064370:Spike Glycoprotein, Coronavirus
COVID-19 Adaptive immunity Immunology