Multimechanistic Monoclonal Antibody Combination Targeting Key Staphylococcus aureus Virulence Determinants in a Rabbit Model of Prosthetic Joint Infection

Author:

Mao Yanjie12,Valour Florent134,Nguyen Nhu T. Q.1,Doan Thien M. N.1,Koelkebeck Holly5,Richardson Christopher6,Cheng Lily I.5,Sellman Bret R.6,Tkaczyk Christine6,Diep Binh An1

Affiliation:

1. Division of HIV, Infectious Diseases, and Global Medicine, Department of Medicine, University of California, San Francisco, San Francisco, California, USA

2. Department of Orthopedic Surgery, Shanghai Jiao Tong University Affiliated Sixth People’s Hospital, Shanghai, People’s Republic of China

3. Department of Infectious Diseases, Hospices Civils de Lyon, Lyon, France

4. CIRI – Centre International de Recherche en Infectiologie, Inserm, U1111, Université Claude Bernard Lyon 1, CNRS, UMR5308, Ecole Normale Supérieure de Lyon, Université Lyon, Lyon, France

5. Translational Sciences, BioPharmaceuticals R&D, AstraZeneca, Gaithersburg, Maryland, USA

6. Discovery Microbiome, Microbial Sciences, BioPharmaceuticals R&D, AstraZeneca, Gaithersburg, Maryland, USA

Abstract

In a rabbit model of methicillin-resistant Staphylococcus aureus prosthetic joint infection (PJI), prophylaxis with AZD6389*—a combination of three monoclonal antibodies targeting alpha-hemolysin, bicomponent cytotoxins (LukSF/LukED/HlgAB/HlgCB), and clumping factor A—resulted in significant reductions in joint swelling, erythema, intra-articular pus, and bacterial burden in synovial tissues and biofilm-associated prosthetic implants compared with isotype-matched control IgG.

Funder

Monahan Foundation

Shanghai Jiao Tong University Affiliated Sixth People's Hospital

College des Enseignants de Maladies Infectieuses et Tropicales

Franco American Commission Fulbright

AstraZeneca

Université Claude Bernard Lyon 1

Publisher

American Society for Microbiology

Subject

Infectious Diseases,Pharmacology (medical),Pharmacology

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