Breakthrough SARS-CoV-2 Infections in the PROVENT Prevention Trial Were Not Associated With AZD7442 (Tixagevimab/Cilgavimab) Resistant Variants.

Background: We report spike protein-based lineage and AZD7442 (tixagevimab/cilgavimab) neutralizing activity of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) variants identified from breakthrough infections in the PROVENT preexposure prophylaxis trial.
Methods: Variants identified from PROVENT participants with reverse-transcription polymerase chain reaction-positive symptomatic illness were phenotypically assessed to determine neutralization susceptibility of variant-specific pseudotyped virus-like particles.
Results: At completion of 6 months' follow-up, no AZD7442-resistant variants were observed in breakthrough coronavirus disease 2019 (COVID-19) cases. SARS-CoV-2 neutralizing antibody titers were similar in breakthrough and nonbreakthrough cases.
Conclusions: Symptomatic COVID-19 breakthrough cases in PROVENT were not due to resistance-associated substitutions in AZD7442 binding sites or lack of AZD7442 exposure.
Clinical Trials Registration: NCT04625725.
Competing Interests: Potential conflicts of interest. M. J. L. reports research support from GSK, Johnson & Johnson, Moderna, and Novavax; consultancy for Dynavax, GSK, Merck & Co, Pfizer, Curevo, and Seqirus; and data safety monitoring board for GSK. A. U. reports honoraria/speaker fees from Sanofi, Merck, Janssen, GSK, and Gilead; and advisory boards for Gilead, Merck, and ViiV/GSK. All other authors are employees of, and hold or may hold stock in, AstraZeneca. All authors have submitted the ICMJE Form for Disclosure of Potential Conflicts of Interest. Conflicts that the editors consider relevant to the content of the manuscript have been disclosed.
(© The Author(s) 2023. Published by Oxford University Press on behalf of Infectious Diseases Society of America.)