SARS-CoV-2 specific antibody and neutralization assays reveal the wide range of the humoral immune response to virus

• Published in: Communications biology Vol. 4; no. 1; pp. 129 - 13
• Main Authors: Dogan, Mikail, Kozhaya, Lina, Placek, Lindsey, Gunter, Courtney, Yigit, Mesut, Hardy, Rachel, Plassmeyer, Matthew, Coatney, Paige, Lillard, Kimberleigh, Bukhari, Zaheer, Kleinberg, Michael, Hayes, Chelsea, Arditi, Moshe, Klapper, Ellen, Merin, Noah, Liang, Bruce Tsan-Tang, Gupta, Raavi, Alpan, Oral, Unutmaz, Derya
• Format: Journal Article
• Language: English
• Published: London Nature Publishing Group UK 29.01.2021; Nature Publishing Group; Nature Portfolio
• Subjects: 13/1; 42/34; 45/44; 631/250/2152/2153/1291; 631/326/2521; 631/326/596/4130; 692/308/575; 96/106; 96/31; Adult; Angiotensin-Converting Enzyme 2 - chemistry; Angiotensin-Converting Enzyme 2 - immunology; Angiotensin-Converting Enzyme 2 - metabolism; Antibodies; Antibodies, Neutralizing - biosynthesis; Antibodies, Neutralizing - chemistry; Antibodies, Viral - biosynthesis; Antibodies, Viral - chemistry; Antibody response; Biomedical and Life Sciences; Convalescence; Coronavirus Nucleocapsid Proteins - chemistry; Coronavirus Nucleocapsid Proteins - immunology; Coronavirus Nucleocapsid Proteins - metabolism; Coronaviruses; COVID-19; COVID-19 - diagnosis; COVID-19 - immunology; COVID-19 - virology; Enzyme-Linked Immunosorbent Assay - methods; Epitopes - chemistry; Epitopes - immunology; Epitopes - metabolism; Female; Genetic Vectors - chemistry; Genetic Vectors - metabolism; Humans; Immune response (humoral); Immune Sera - chemistry; Immunity, Humoral; Immunoglobulin A; Immunoglobulin G; Lentivirus - genetics; Lentivirus - immunology; Life Sciences; Male; Middle Aged; Neutralization Tests; Nucleocapsids; Phosphoproteins - chemistry; Phosphoproteins - immunology; Phosphoproteins - metabolism; Protein Binding; Protein folding; Proteins; Public health; Receptors, Virus - chemistry; Receptors, Virus - immunology; Receptors, Virus - metabolism; SARS-CoV-2 - drug effects; SARS-CoV-2 - immunology; SARS-CoV-2 - pathogenicity; Severe acute respiratory syndrome coronavirus 2; Severity of Illness Index; Spike Glycoprotein, Coronavirus - chemistry; Spike Glycoprotein, Coronavirus - immunology; Spike Glycoprotein, Coronavirus - metabolism; Spike protein; Survival Analysis; Vaccine development; Vaccines
• ISSN: 2399-3642; 2399-3642
• DOI: 10.1038/s42003-021-01649-6

Development of antibody protection during SARS-CoV-2 infection is a pressing question for public health and for vaccine development. We developed highly sensitive SARS-CoV-2-specific antibody and neutralization assays. SARS-CoV-2 Spike protein or Nucleocapsid protein specific IgG antibodies at titers more than 1:100,000 were detectable in all PCR+ subjects ( n  = 115) and were absent in the negative controls. Other isotype antibodies (IgA, IgG1-4) were also detected. SARS-CoV-2 neutralization was determined in COVID-19 and convalescent plasma at up to 10,000-fold dilution, using Spike protein pseudotyped lentiviruses, which were also blocked by neutralizing antibodies (NAbs). Hospitalized patients had up to 3000-fold higher antibody and neutralization titers compared to outpatients or convalescent plasma donors. Interestingly, some COVID-19 patients also possessed NAbs against SARS-CoV Spike protein pseudovirus. Together these results demonstrate the high specificity and sensitivity of our assays, which may impact understanding the quality or duration of the antibody response during COVID-19 and in determining the effectiveness of potential vaccines. Using SARS-CoV-2-specific antibody- and neutralization assays, Dogan et al find that hospitalized individuals show higher IgG antibody responses and higher neutralization titers compared to outpatient or convalescent plasma donors, providing insights into the host humoral response to SARS CoV-2.