Characterisation of anti-alpha toxin antibody levels and colonisation status after administration of an investigational human monoclonal antibody, MEDI4893, against Staphylococcus aureus alpha toxin

Clinical & Translational Immunology
Alexey RuzinHasan S Jafri

Abstract

MEDI4893 is a novel, long-acting human monoclonal antibody targeting Staphylococcus aureus (SA) alpha toxin (AT). This report presents the results of the exploratory analyses from a randomised phase 1 dose-escalation study in healthy human subjects receiving single intravenous MEDI4893 doses or placebo. Anti-AT antibodies and AT expression were measured as described previously. Nasal swabs were analysed by culture and PCR. Data were summarised by treatment groups and visits by using SAS System Version 9.3. Subjects receiving 2250 or 5000 mg of MEDI4893 had the highest serum anti-AT neutralising antibody (NAb) levels: approximately 180- to 240-, 70- to 100- and sevenfold to 10-fold higher than respective baseline levels at peak, 30 and 360 days, respectively. In these subjects, levels of serum anti-AT NAbs were >3.2 International Units (IU) mL-1 for at least 211 days. In the upper respiratory tract, anti-AT NAb levels increased with MEDI4893 dose. No apparent effect of MEDI4893 on SA nasal colonisation, hla gene sequence or AT expression was observed. Five AT variants were detected, their lytic activity was fully neutralised by MEDI4893. Our results indicate that (1) MEDI4893 administration at 2250 and 5000 mg would provide effe...Continue Reading

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Citations

Apr 6, 2019·Current Opinion in Infectious Diseases·Michael P MotleyBettina C Fries
Mar 11, 2020·Antimicrobial Agents and Chemotherapy·Omari Jones-NelsonBret R Sellman
May 29, 2020·Antioxidants & Redox Signaling·Viktoria Rungelrath, Frank R DeLeo
Mar 17, 2020·Biotechnology Journal·Elizabeth Huiwen ThamIn Young Hwang
Jun 3, 2021·Vaccines·Pietro Speziale, Giampiero Pietrocola
Aug 5, 2021·ACS Infectious Diseases·Erin M DuffyRichard A Alm
Jul 2, 2021·Emerging Topics in Life Sciences·Derry K MercerDouglas Fraser-Pitt

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Methods Mentioned

BETA
PCR
ELISA

Clinical Trials Mentioned

NCT01769417

Software Mentioned

Prism
SAS System

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