Pseudomonas aeruginosa Bacteremic Patients Exhibit Nonprotective Antibody Titers Against Therapeutic Antibody Targets PcrV and Psl Exopolysaccharide

The Journal of Infectious Diseases
Joshua T ThadenAntonio DiGiandomenico

Abstract

The type 3 secretion protein PcrV and Psl exopolysaccharide are promising therapeutic antibody targets against Pseudomonas aeruginosa. We examined P. aeruginosa bloodstream infection (BSI) isolates for the ability to express PcrV and Psl and evaluated corresponding patient serum for active titers to these targets. We identified 114 patients with acute P. aeruginosa BSI; 56 cases were accompanied by acute sera. Serum was evaluated for PcrV- and Psl-specific immunoglobulin G (IgG) and for cytotoxicity and opsonophagocytosis. Isolates were evaluated for susceptibility to antibiotics, expression of PcrV and Psl, and susceptibility to the anti-PcrV/Psl bispecific antibody and clinical candidate MEDI3902. In-hospital mortality for patients with P. aeruginosa BSI was 39%. A total of 26% of isolates were resistant to ≥3 antibiotic classes. Although PcrV and/or Psl were detected in 99% of isolates, a majority of patients lacked active titers to PcrV (100%) and Psl (98%). In addition, MEDI3902 was active against all tested isolates. A vast majority of P. aeruginosa BSI isolates express PcrV and Psl; however, patient sera most often lacked IgG and functionally active responses to these targets. These results suggest that therapies directe...Continue Reading

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Citations

Dec 31, 2016·International Journal of Molecular Sciences·Fa YangWeijun Qin
Nov 24, 2017·Scientific Reports·Valerie A RayAntonio DiGiandomenico
Jul 18, 2018·Molecules : a Journal of Synthetic Chemistry and Natural Product Chemistry·Cinzia ColomboLuigi Lay
Oct 22, 2020·Research : a Science Partner Journal·Zifang ShangWei Huang
Dec 4, 2020·Expert Review of Anti-infective Therapy·Marios KarvouniarisGaryphallia Poulakou
Sep 4, 2020·Expert Opinion on Drug Discovery·Xiaolong ShaoXin Deng
Apr 2, 2021·Nature Communications·Henrik AlmbladJoe Jonathan Harrison

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