Prophylactic and therapeutic protection of human IgG purified from sera containing anti-exotoxin A titers against pneumonia caused by Pseudomonas aeruginosa

ABSTRACT

Antibodies are effective alternative tools to combat infections caused by Pseudomonas aeruginosa (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 in vitro. 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.

KEYWORDS:

• Pseudomonas aeruginosa
• exotoxin A
• human intravenous immunoglobulin
• therapy

Supplemental data

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Author contributions

QZ, XW and JG designed, coordinated and supervised the research. JZ and WC performed the major experiments. BY provided the serum samples. FY developed the pneumonia model. CG and XC collected clinical samples. LZ and HG assisted the Luminex measurement. JZ and JG wrote the manuscript. All authors revised the manuscript and contributed to improving the paper; all authors read and approved the final manuscript.

Disclosure of potential conflicts of interest

No conflict of interest exits in the submission of this manuscript.

Additional information

Funding

This work was supported by the National Natural Science Foundation of China (NSFC, Grant No. 81571621) and National Natural Science Foundation of Chongqing (CSTC2016JCYJA0080)National Natural Science Foundation of China [81571621];Natural Science Foundation of Chongqing [CSTC2016JCYJA0080].