MEDI3902 Correlates of Protection against Severe Pseudomonas aeruginosa Pneumonia in a Rabbit Acute Pneumonia Model

Antimicrobial Agents and Chemotherapy
Hoan N LeBinh An Diep

Abstract

Pseudomonas aeruginosa is among the most formidable antibiotic-resistant pathogens and is a leading cause of hospital-associated infections. With dwindling options for antibiotic-resistant infections, a new paradigm for treatment and disease resolution is required. MEDI3902, a bispecific antibody targeting the P. aeruginosa type III secretion (T3S) protein PcrV and Psl exopolysaccharide, was previously shown to mediate potent protective activity in murine infection models. With the current challenges associated with the clinical development of narrow-spectrum agents, robust preclinical efficacy data in multiple animal species are desirable. Here, we sought to develop a rabbit P. aeruginosa acute pneumonia model to further evaluate the activity of MEDI3902 intervention. In the rabbit model of acute pneumonia, prophylaxis with MEDI3902 exhibited potent dose-dependent protection, whereas those receiving control IgG developed fatal hemorrhagic necrotizing pneumonia between 12 and 54 h after infection. Blood biomarkers (e.g., partial pressure of oxygen [pO2], partial pressure of carbon dioxide [pCO2], base excess, lactate, and creatinine) were grossly deranged for the vast majority of control IgG-treated animals but remained within ...Continue Reading

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Citations

Nov 27, 2018·Respirology : Official Journal of the Asian Pacific Society of Respirology·Kerry-Ann F O'GradyKeith Grimwood
Apr 6, 2019·Current Opinion in Infectious Diseases·Michael P MotleyBettina C Fries
May 25, 2021·Frontiers in Immunology·Jiabing MaCheng Qian
Mar 14, 2020·Infectious Disorders Drug Targets·Gerard M RajMangaiarkkarasi Adhimoolam

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Methods Mentioned

BETA
reverse transcription-PCR
PCRs
PCR

Clinical Trials Mentioned

NCT02696902

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