A scalable serology solution for profiling humoral immune responses to SARS-CoV-2 infection and vaccination

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DOI

https://doi.org/10.1002/cti2.1380

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

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Collection(s)

Communicable diseases

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