Serum AZD7442 (tixagevimab-cilgavimab) Concentrations and IC Values Predict SARS-CoV-2 Neutralising Antibody Titres

Overview

Journal Clin Transl Immunology

Specialty Allergy & Immunology

Date 2024 Jun 14

PMID 38873124

Authors

Lindsay E Clegg

Oleg Stepanov

Sam Matthews

Tom White

Seth Seegobin

Steven Thomas

Kevin M Tuffy

Mats Nagard

Mark T Esser

Katie Streicher

Taylor S Cohen

Anastasia A Aksyuk

Affiliations

Soon will be listed here.

Abstract

Objectives: The evolution of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) necessitates rapid methods for assessing monoclonal antibody (mAb) potency against emerging variants. Authentic virus neutralisation assays are considered the gold standard for measuring virus-neutralising antibody (nAb) titres in serum. However, authentic virus-based assays pose inherent practical challenges for measuring nAb titres against emerging SARS-CoV-2 variants (e.g. storing infectious viruses and testing at biosafety level-3 facilities). Here, we demonstrate the utility of pseudovirus neutralisation assay data in conjunction with serum mAb concentrations to robustly predict nAb titres in serum.

Methods: SARS-CoV-2 nAb titres were determined via authentic- and lentiviral pseudovirus-based neutralisation assays using serological data from three AZD7442 (tixagevimab-cilgavimab) studies: PROVENT (NCT04625725), TACKLE (NCT04723394) and a phase 1 dose-ranging study (NCT04507256). AZD7442 serum concentrations were assessed using immunocapture. Serum-based half-maximal inhibitory concentration (IC) values were derived from pseudovirus nAb titres and serum mAb concentrations, and compared with IC measurements.

Results: nAb titres measured via authentic- and lentiviral pseudovirus-based neutralisation assays were strongly correlated for the ancestral SARS-CoV-2 virus and SARS-CoV-2 Alpha. Serum AZD7442 concentrations and pseudovirus nAb titres were strongly correlated for multiple SARS-CoV-2 variants with all Spearman correlation coefficients ≥ 0.78. Serum-based IC values were similar to IC values for AZD7442, for ancestral SARS-CoV-2 and Alpha, Delta, Omicron BA.2 and Omicron BA.4/5 variants.

Conclusions: These data highlight that serum mAb concentrations and pseudovirus IC values can be used to rapidly predict nAb titres in serum for emerging and historical SARS-CoV-2 variants.

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