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Prophylactic and Therapeutic Protection of Human IgG Purified from Sera Containing Anti-exotoxin A Titers Against Pneumonia Caused by

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Date 2019 May 23
PMID 31116632
Citations 1
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Abstract

Antibodies are effective alternative tools to combat infections caused by (PA), especially multi-drug-resistant PA. Thus, to solve the urgent need for an anti-PA antibody drug, we hypothesized that anti-PA intravenous immunoglobulins could be a practical attempt. Exotoxin A (ETA) is one of the most important factors for PA infection and is also a critical target for the development of immune interventions. In this study, a total of 320 sera were collected from healthy volunteers. The concentration of ETA-specific antibodies was determined by a Luminex-based assay and then purified by affinity chromatography. The purified IgGs were able to neutralize the cytotoxicity of ETA . We showed they had a prophylactic and therapeutic protective effect in PA pneumonia and ETA toxemia models. In addition, administration of nonspecific IgGs also provided partial protection. Collectively, our results provide additional evidence for IVIG-based treatment of infections caused by multi-drug-resistant PA and suggest that patients at high risk of PA pneumonia could be prophylactically treated with anti-ETA IgGs or even with nonspecific IgGs.

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References
1.
Jiang M, Yao J, Feng G . Protective effect of DNA vaccine encoding pseudomonas exotoxin A and PcrV against acute pulmonary P. aeruginosa Infection. PLoS One. 2014; 9(5):e96609. PMC: 4006881. DOI: 10.1371/journal.pone.0096609. View

2.
Katoh H, Yasumoto H, Shimizu M, Hamaoka S, Kinoshita M, Akiyama K . IV Immunoglobulin for Acute Lung Injury and Bacteremia in Pseudomonas aeruginosa Pneumonia. Crit Care Med. 2015; 44(1):e12-24. DOI: 10.1097/CCM.0000000000001271. View

3.
Ali S, Yu X, Robbie G, Wu Y, Shoemaker K, Yu L . Phase 1 study of MEDI3902, an investigational anti-Pseudomonas aeruginosa PcrV and Psl bispecific human monoclonal antibody, in healthy adults. Clin Microbiol Infect. 2018; 25(5):629.e1-629.e6. DOI: 10.1016/j.cmi.2018.08.004. View

4.
Armstrong S, Yates S, Merrill A . Insight into the catalytic mechanism of Pseudomonas aeruginosa exotoxin A. Studies of toxin interaction with eukaryotic elongation factor-2. J Biol Chem. 2002; 277(48):46669-75. DOI: 10.1074/jbc.M206916200. View

5.
Sawa T, Ito E, Nguyen V, Haight M . Anti-PcrV antibody strategies against virulent Pseudomonas aeruginosa. Hum Vaccin Immunother. 2014; 10(10):2843-52. PMC: 5443083. DOI: 10.4161/21645515.2014.971641. View