Serum AZD7442 (tixagevimab–cilgavimab) concentrations and in vitroIC50 values predict SARS‐CoV‐2 neutralising antibody titres

• DOI: 10.1002/cti2.1517
• Publication Date: 2024-06-14T01:10:07Z
• Authors: Lindsay E Clegg; Oleg Stepanov; Sam Matthews; Tom White; Seth Seegobin; Steven Thomas; Kevin M Tuffy; Mats Någård; Mark T Esser; Katie Streicher; Taylor S Cohen; Anastasia A Aksyuk
• Keywords: pseudovirus assay; SARS‐CoV‐2 neutralising antibody titres; Original Article; COVID‐19 monoclonal antibodies; authentic virus assay; Immunologic diseases. Allergy; RC581-607; AZD7442 (tixagevimab–cilgavimab); pharmacokinetics

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 measuring virus‐neutralising (nAb) titres in serum. However, authentic virus‐based pose inherent practical challenges nAb SARS‐CoV‐2 variants (e.g. storing infectious viruses and testing at biosafety level‐3 facilities). Here, we demonstrate utility pseudovirus assay data conjunction with serum mAb concentrations to robustly predict Methods were determined via authentic‐ lentiviral pseudovirus‐based using serological from three AZD7442 (tixagevimab–cilgavimab) studies: PROVENT (NCT04625725), TACKLE (NCT04723394) a phase 1 dose‐ranging study (NCT04507256). assessed immunocapture. Serum‐based half‐maximal inhibitory concentration (IC 50 ) values derived concentrations, compared vitro IC measurements. Results measured strongly correlated ancestral Alpha. Serum multiple all Spearman correlation coefficients ≥ 0.78. similar AZD7442, Alpha, Delta, Omicron BA.2 BA.4/5 Conclusions These highlight that can be used rapidly historical