A scalable serology solution for profiling humoral immune responses to SARS-CoV-2 infection and vaccination
- DOI
- Language of the publication
- English
- Date
- 2022-03-23
- Type
- Article
- Author(s)
- Colwill, Karen
- Arnold, Corey
- Rathod, Bhavisha
- Abe, Kento T.
- Wang, Jenny H.
- Pasculescu, Adrian
- Maltseva, Mariam
- Rocheleau, Lynda
- Pelchat, Martin
- Fazel-Zarandi, Mahya
- Iskilova, Mariam
- Barrios-Rodiles, Miriam
- Bennett, Linda
- Yau, Kevin
- Cholette, François
- Mesa, Christine
- Li, Angel X.
- Paterson, Aimee
- Hladunewich, Michelle A.
- Goodwin, Pamela J.
- Wrana, Jeffrey L.
- Drews, Steven J.
- Mubareka, Samira
- McGeer, Allison J.
- Kim, John
- Langlois, Marc-André
- Gingras, Anne-Claude
- Durocher, Yves
- Langlois, Marc-Andre
- Galipeau, Yannick
- Stuible, Matthew
- Publisher
- Australian and New Zealand Society for Immunology
Abstract
OBJECTIVES: Antibody testing against severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) has been instrumental in detecting previous exposures and analyzing vaccine-elicited immune responses. Here, we describe a scalable solution to detect and quantify SARS-CoV-2 antibodies, discriminate between natural infection- and vaccination-induced responses, and assess antibody-mediated inhibition of the spike-angiotensin converting enzyme 2 (ACE2) interaction. METHODS: We developed methods and reagents to detect SARS-CoV-2 antibodies by enzyme-linked immunosorbent assay (ELISA). The main assays focus on the parallel detection of immunoglobulin (Ig)Gs against the spike trimer, its receptor binding domain (RBD) and nucleocapsid (N). We automated a surrogate neutralisation (sn)ELISA that measures inhibition of ACE2-spike or -RBD interactions by antibodies. The assays were calibrated to a World Health Organization reference standard. RESULTS: Our single-point IgG-based ELISAs accurately distinguished non-infected and infected individuals. For seroprevalence assessment (in a non-vaccinated cohort), classifying a sample as positive if antibodies were detected for ≥ 2 of the 3 antigens provided the highest specificity. In vaccinated cohorts, increases in anti-spike and -RBD (but not -N) antibodies are observed. We present detailed protocols for serum/plasma or dried blood spots analysis performed manually and on automated platforms. The snELISA can be performed automatically at single points, increasing its scalability. CONCLUSIONS: Measuring antibodies to three viral antigens and identify neutralising antibodies capable of disrupting spike-ACE2 interactions in high-throughput enables large-scale analyses of humoral immune responses to SARS-CoV-2 infection and vaccination. The reagents are available to enable scaling up of standardised serological assays, permitting inter-laboratory data comparison and aggregation.
Subject
- Health,
- Coronavirus diseases,
- Screening (Medicine)
Rights
Pagination
1-22
Peer review
Yes
Identifiers
- PubMed ID
- 35356067
- ISSN
- 2050-0068
Article
- Journal title
- Clinical & Translational Immunology
- Journal volume
- 11
- Article number
- E1380