CVR - Coronavirus Vaccines R&D Roadmap

Milestone
2.6.i

Standardized assays

In progress

Develop mechanisms to standardize CoP assays to facilitate comparability across vaccine platforms and modes of administration.

Progress Highlights

Kemp 2023 and Knezevic 2022 highlighted the variability in SARS-CoV-2 antibody assays and demonstrated the feasibility of harmonizing these using the WHO International Standard. 

Kemp 2023 found that, while neutralization assays provide the most direct measure of protection, binding immunoassays could serve as practical proxies, given their high correlation with neutralization titers.

Cabrera-Alvargonzalez 2024 conducted a comparative study of eleven commercial antibody assays and their correlation with neutralization assays. They found high agreement among immunoassays, particularly those targeting the spike protein, which aligns with vaccine-induced immunity. However, they stressed the importance of updating targets and improving standardization to account for emerging variants, which can impact assay sensitivity and specificity.

Bladh 2025 found that spike-specific IgA/SIgA measurements showed strong cross-assay and within-compartment agreement, especially after normalizing to total IgA, however with saliva swabs underperforming relative to passive drool and Salivette, in a study evaluating concordance across mucosal sampling methods (nasal swab, Nasosorption, Salivette, saliva swab, passive drool) and assays (commercial ECL; two in-house ELISAs) for detecting spike-specific IgA/SIgA in mucosal secretions,  Nasal samples had markedly higher normalized IgA than saliva (>3×), and IgA tracked SIgA closely, supporting nasal sampling when feasible, and the use of IgA alone as a practical proxy.

Marchant 2024 describes a meeting in February 2023 convened by the International Alliance for Biological Standardization, the European Plotkin Institute for Vaccinology, and Vaccinopolis to discuss CoPs against COVID-19. The objective was to assess existing evidence, formulate conclusions, and identify gaps in knowledge.

The meeting determined research priorities, including 

  • Clinical studies should focus on defining CoPs for mucosal immunity to evaluate intranasal vaccines.
  • Immunobridging studies should include cellular immune responses in addition to antibody measurements.
  • Global coordination is needed to ensure harmonized CoP definitions and standardized immunoassays for vaccine comparison.

Azizi 2024 describes establishment of the CEPI-Centralized Laboratory Network (CLN) to standardize immunological assays globally, enabling consistent evaluation of COVID-19 vaccines and ensuring data reliability across facilities.