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

J Infect Dis. 2023 Oct 18;228(8):1055-1059. doi: 10.1093/infdis/jiad210.

Abstract

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.

Keywords: AZD7442; COVID-19; SARS-CoV-2; cilgavimab; monoclonal antibody; tixagevimab; viral neutralization; viral resistance.

Publication types

  • Clinical Trial
  • Research Support, U.S. Gov't, Non-P.H.S.
  • Research Support, U.S. Gov't, P.H.S.
  • Research Support, Non-U.S. Gov't

MeSH terms

  • Antibodies, Neutralizing
  • Breakthrough Infections
  • COVID-19* / prevention & control
  • Humans
  • SARS-CoV-2

Substances

  • Antibodies, Neutralizing
  • cilgavimab
  • cilgavimab and tixagevimab drug combination
  • tixagevimab

Supplementary concepts

  • COVID-19 breakthrough infections

Associated data

  • ClinicalTrials.gov/NCT04625725

Grants and funding