Journal Article Ppublish
PubMed: 39442367 DOI: 10.1016/j.ebiom.2024.105417
Cilgavimab and tixagevimab as pre-exposure prophylaxis in vaccine non-responder kidney transplant recipients during a period of prevalent SARS-CoV-2 BA.2 and BA.4/5 variants-a prospective cohort study (RESCUE-TX).
EBioMedicine 109:105417
Authors: Roman Reindl-Schwaighofer, Andreas Heinzel, Lukas Raab, Robert Strassl, Carsten T Herz, Florina Regele, Konstantin Doberer, Oliver Helk, Paul Spechtl, Constantin Aschauer, Karin Hu, Rahel Jagoditsch, Bianca Reiskopf, Georg A Böhmig, Bernhard Benka, Benedikt Mahr, Karin Stiasny, Lukas Weseslindtner, Michael Kammer, Thomas Wekerle, Rainer Oberbauer
Affiliations
- Division of Nephrology and Dialysis, Department of Medicine III, Medical University of Vienna, Vienna, Austria.
- Department of Laboratory Medicine, Division of Clinical Virology, Medical University of Vienna, Vienna, Austria.
- Austrian Agency for Health and Food Safety (AGES), Vienna, Austria.
- Astra Zeneca Medical, Vienna, Austria.
- Center for Virology, Medical University of Vienna, Vienna, Austria.
- Division of Nephrology and Dialysis, Department of Medicine III, Medical University of Vienna, Vienna, Austria; Center for Medical Data Science, Institute for Clinical Biometrics, Medical University of Vienna, Vienna, Austria.
- Division of Transplantation, Department of General Surgery, Medical University of Vienna, Vienna, Austria.
- Division of Nephrology and Dialysis, Department of Medicine III, Medical University of Vienna, Vienna, Austria.
Abstract
BACKGROUND
The response to severe acute respiratory syndrome coronavirus type 2 (SARS-CoV-2) vaccination is severely impaired in patients on maintenance immunosuppression after kidney transplantation.
METHODS
We conducted a prospective cohort study of 194 kidney transplant recipients (KTR) who exhibited no response to SARS-CoV-2 vaccinations (i.e., SARS-CoV-2 spike protein antibodies ≤264 U/mL) and had no prior documented infection. Patients received 300 mg of cilgavimab/tixagevimab as SARS-CoV-2 pre-exposure prophylaxis (PrEP) between March 4, 2022, and May 3, 2022 and were contrasted to a matched cohort of 186 KTRs also without immunization again defined as SARS-CoV-2 spike protein antibodies ≤264 U/mL and no documented prior infection. The primary outcome was the serum kinetics of cilgavimab/tixagevimab, the secondary endpoints were time to SARS-CoV-2 breakthrough infection, severity of disease and variant specific live viral in vitro neutralization tests of patient sera.
FINDINGS
Longitudinal serum level monitoring showed a half-life of 91 days for both antibodies (95% CI 86-95 days for cilgavimab and 85-96 days for tixagevimab) in KTRs. In vitro neutralization tests showed effectiveness against the BA.2 omicron subvariant but not BA.5. The cumulative incidence of SARS-CoV-2 infections until May 15, 2022, (BA.2 dominance) was 15/194 vs 36/186 in the PrEP and control group respectively (OR = 0.35, 95% CI 0.18-0.66) but was not different thereafter (BA.4/5 dominance). The number of severe infections during the BA.2 period was lower in the prophylaxis than in the control group (OR = 0.37, 95% CI 0.17-0.79).
INTERPRETATION
This study showed that SARS-CoV-2 PrEP with cilgavimab/tixagevimab demonstrated clinical effectiveness against variants that are neutralised (BA.2) but not against BA.4/5.
FUNDING
This study was funded by the Medical University of Vienna and an unrestricted grant from AstraZeneca (ESR-21-21585).
MeSH
Sars-Cov-2, Neutralization Tests, Serum, Vaccines, Antibodies, Pre-Exposure Prophylaxis, Biomedical Research, Cohort Studies, Kidney, Vaccination, Transplants, Severe Acute Respiratory Syndrome-Related Coronavirus, Infections, Non-Responder