Serum AZD7442 (tixagevimab-cilgavimab) concentrations and in vitro IC50 values predict SARS-CoV-2 neutralising antibody titres

被引：1

作者：

Clegg, Lindsay E. ^{[1
]}

Stepanov, Oleg ^{[2
]}

Matthews, Sam ^{[3
]}

White, Tom ^{[3
]}

Seegobin, Seth ^{[3
]}

Thomas, Steven ^{[4
]}

Tuffy, Kevin M. ^{[5
]}

Nagard, Mats ^{[1
]}

Esser, Mark T. ^{[6
]}

Streicher, Katie ^{[5
]}

Cohen, Taylor S. ^{[6
]}

Aksyuk, Anastasia A. ^{[5
]}

机构：

[1] AstraZeneca, Clin Pharmacol & Quantitat Pharmacol, Clin Pharmacol & Safety Sci, R&D, Gaithersburg, MD USA

[2] AstraZeneca, Clin Pharmacol & Quantitat Pharmacol, Clin Pharmacol & Safety Sci, R&D, Cambridge, England

[3] AstraZeneca, Biometr Vaccines & Immune Therapies, BioPharmaceut R&D, Cambridge, England

[4] AstraZeneca, Biometr Vaccines & Immune Therapies, BioPharmaceut R&D, Durham, NC USA

[5] AstraZeneca, Translat Med Vaccines & Immune Therapies, BioPharmaceut R&D, Gaithersburg, MD 20878 USA

[6] AstraZeneca, Vaccines & Immune Therapies, Biopharmaceut R&D, Gaithersburg, MD USA

来源：

CLINICAL & TRANSLATIONAL IMMUNOLOGY | 2024年 / 13卷 / 06期

关键词：

authentic virus assay; AZD7442 (tixagevimab-cilgavimab); COVID-19 monoclonal antibodies; pharmacokinetics; pseudovirus assay; SARS-CoV-2 neutralising antibody titres;

D O I：

10.1002/cti2.1517

中图分类号：

R392 [医学免疫学]; Q939.91 [免疫学];

学科分类号：

100102 ;

摘要：

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 (IC50) values were derived from pseudovirus nAb titres and serum mAb concentrations, and compared with in vitro IC50 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 IC50 values were similar to in vitro IC50 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 in vitro IC50 values can be used to rapidly predict nAb titres in serum for emerging and historical SARS-CoV-2 variants.

引用

页数：15