2023-01-31-世界卫生组织-WHO_BS_2023.2450_WHO_proposed_expansion_of_Reference_Panel_for_anti-SARS-CoV-2_variants_of_concern_immunoglobulin_43页_913kb

Summary of the WHO Collaborative Study on Expansion of the Reference Panel for Antibodies to SARS-CoV-2 Variants of Concern

Core Content

This document outlines a collaborative study conducted by the Expert Committee on Biological Standardization (ECBS) to evaluate the inclusion of two new plasma pools into the First WHO International Reference Panel (IRP) for antibodies to SARS-CoV-2 variants of concern (VOC). The study was aimed at expanding the reference panel to include samples from individuals infected with the Gamma and Omicron variants, which were dominant at the time of the study.

Main Objectives

• Characterise the reactivity and performance of two candidate plasma pools (Gamma and Omicron) in various serological assay systems.
• Assess the stability of the existing IRP members and the candidate preparations under different thermal conditions.
• Provide recommendations to the ECBS on the inclusion of the Gamma and Omicron plasma pools into the WHO IRP.

Key Information

Candidate Preparations

• Gamma (NIBSC code 22/126): A pool of plasma from 6 unvaccinated donors in Brazil, collected during the peak of the Gamma variant in 2021.
• Omicron (NIBSC code 22/128): A pool of plasma from 9 unvaccinated donors in South Africa, collected in December 2021, with infection confirmed as Omicron B.1.1.529.

Both preparations were freeze-dried and stored in glass DIN ampoules, with the Gamma sample pre-treated with INTERCEPT and the Omicron sample processed using solvent-detergent treatment.

Existing WHO IRP Members

• pre-VOC (NIBSC 21/296): A pool of plasma from 4 unvaccinated individuals in the USA, collected between September and December 2020.
• Alpha (NIBSC 21/300): A pool of plasma from 3 unvaccinated individuals in the UK, collected in January 2021.
• Delta (NIBSC 21/312): A pool of sera from 19 individuals in Kenya, infected with the Delta variant.

Study Design and Methods

• The study was conducted between September 2022 and January 2023.
• Participants were asked to perform three independent assays, including neutralisation tests and binding antibody assays.
• Neutralisation assays were conducted using actual SARS-CoV-2 virus, pseudotyped virus, or a surrogate neutralisation test.
• Binding assays were performed using in-house ELISA methods and a Luminex-based multiplex assay, targeting Spike, Receptor Binding Domain (RBD), and Nucleoprotein (N) antigens.

Assay Results

• Neutralisation Assays: Both Gamma and Omicron samples showed strong neutralising activity against the respective variants, with no evidence of differential potency against autologous virus for Gamma. Omicron had the lowest titre against early isolates but showed high potency against Omicron isolates.
• Binding Assays: The Gamma sample showed similar potency to the existing Alpha and pre-VOC samples, while the Omicron sample had lower potency against early isolates but higher against Omicron. IgM responses were only detected by one laboratory.
• Concordance: There was good agreement in the ranking of samples among participants, with the First WHO IS for anti-SARS-CoV-2 VOC (VOC-01) consistently showing the highest potency.

Stability Study

• An accelerated thermal degradation study was conducted on the IRP members and candidate preparations at temperatures of -20°C, +4°C, +20°C, +37°C, and +45°C.
• Potency was assessed relative to the baseline (-20°C) using pseudotyped virus-based neutralisation assays.
• The results showed no loss of potency up to at least two weeks, even at high temperatures (45°C), although long-term stability could not be predicted from the data.

Conclusion

The study supports the proposal to expand the WHO IRP for antibodies to SARS-CoV-2 VOC to include the Gamma and Omicron plasma pools. The data from the collaborative study, including reactivity and stability, indicate that these preparations are suitable for inclusion. No unitage is assigned to the IRP preparation, but instructions for use will reference the geometric mean of the potencies of the panel members relative to the Second WHO IS for anti-SARS-CoV-2 immunoglobulins (21/340) for early isolates and the First WHO IS for antibodies to SARS-CoV-2 VOC (21/338) for Omicron-targeting assays.