Technical guidance for antigenic SARS-CoV-2 monitoring

Technical guidance

European Centre for Disease Prevention and Control/World Health Organization Regional Office for Europe. Technical guidance for
antigenic SARS-CoV-2 monitoring. June 2022. Stockholm/Copenhagen; ECDC/WHO Regional Office for Europe: 2022.

This document provides technical guidance to laboratories, microbiology experts and relevant stakeholders in making decisions on establishing or scaling up capability and capacity to isolate and antigenically characterise circulating SARS-CoV-2 variants, and in making decisions on which methods to use.

The objective of this document is to provide guidance on sampling for virus characterisation, and present available methods for isolation and antigenic characterisation of circulating SARS-CoV-2 viruses. The document also outlines quality assessment issues, as well as practical considerations on virus sharing, support for the laboratories and data sharing.

Executive summary

  • New SARS-CoV-2 variants of interest and concern have continued to emerge in the first few months of 2022 and monitoring their circulation in all countries through genomic surveillance remains important.
  • The variants of interest and concern identified through genomic surveillance need to be characterised and assessed through antigenic characterisation of the viruses.
  • Antigenic characterisation of SARS-CoV-2 variants is essential for evaluation of vaccine efficacy, selecting appropriate virus strain(s) for vaccine development and evaluating vaccine immunogenicity as well as for monitoring resistance to monoclonal antibody (mAb)-based antiviral treatments.
  • Specimens originating from sentinel surveillance systems, as well as from targeted testing e.g. from immunocompromised patients, representing circulating SARS-CoV-2 (sub)lineages should be selected for further antigenic characterisation.
  • SARS-CoV-2 virus isolation from clinical materials should be performed in BSL3 laboratories.
  • Cell culture-adapted mutations during virus propagation present a challenge in antigenic characterisation as well as other analyses. Deep sequencing of the viruses pre- and post-isolation will help to detect any possible cell culture-adapted mutations. Sequencing should be of sufficient depth to detect the emergence of minor variants in which virus key features may have been ablated (e.g. the S1/S2 furin-cleavage site in spike).
  • Antigenic properties of SARS-CoV-2 variants can be characterised using techniques such as plaque reduction neutralisation, microneutralisation and pseudovirus neutralisation assay. The antigenic cartography method is used for visualisation of antigenic properties.
  • Standardisation and uniform laboratory methodologies and standardised output formats are key to be able to robustly interpret and compare data between studies so that national and international public health policies can be correctly informed.
  • Laboratories should use antigenic characterisation to monitor resistance of circulating new variants to monoclonal antibody (mAb)-based antiviral treatments.
  • Several WHO European Region countries have capacity for SARS-CoV-2 isolation and antigenic characterisation.
  • ECDC, as well as WHO reference laboratories for COVID-19 can provide support to countries that do not have capacity to perform virus isolation in BSL3 laboratories and/or antigenic characterisation.
  • Rapid sharing of clinical specimens and/or virus isolates and antigenic data is crucial when a new variant with potential antigenic drift emerges.
  • Antigenic data should be shared immediately with ECDC, WHO Regional Office for Europe and European surveillance networks.
  • Shipments of specimens to reference laboratories can be supported and expedited through the WHO shipment mechanism.