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ABSTRACT
The PcrV cap structure of the type III secretory apparatus of Pseudomonas aeruginosa is a vaccine target. Human immunoglobulin G (IgG) molecules extracted from sera containing high or low anti-PcrV titers were tested for their effects against P. aeruginosa pneumonia in a mouse model. Among 198 volunteers, we selected the top 10 high anti-PcrV titer sera and the bottom 10 low anti-PcrV titer sera and extracted the IgG fraction from each serum sample. First, we examined the effects of the IgG against virulent P. aeruginosa. A lethal dose of P. aeruginosa premixed with saline, low titer human IgG, high titer human IgG, or rabbit-derived polyclonal anti-PcrV IgG was intratracheally administered into the lungs of mice, and their survival and lung inflammation were evaluated for 24 h. The high anti-PcrV titer human IgG had a prophylactic effect. Next, the prophylactic effects of intravenous administration of extracted and pooled high or low anti-PcrV titer human IgG were examined. Here, prophylactic intravenous administration of pooled high anti-PcrV titer human IgG, which showed binding capacity to P. aeruginosa PcrV, was more effective than the administration of its low titer pooled equivalent, and the measured physiological and inflammatory parameters correlated with the anti-PcrV titer levels. This result indirectly implies that high anti-PcrV titers in blood can help to protect against virulent P. aeruginosa infections. In addition, the IgG fractions from such high titer sera have potential to be a source of specific intravenous immunoglobulin products for passive vaccination against virulent P. aeruginosa infections.
Abbreviations
| Anti-PcrV rab-IgG | = | rabbit-derived polyclonal anti-PcrV IgG |
| CFUs | = | colony forming units |
| E. coli | = | Escherichia coli |
| high titer hu-IgG | = | human IgG with high anti-PcrV titer |
| low titer hu-IgG | = | human IgG with low anti-PcrV titer |
| IVIG | = | intravenous immunoglobulin |
| MDRP | = | multidrug resistant Pseudomonas aeruginosa |
| MPO | = | myeloperoxidase |
| OD | = | optical density |
| PBS | = | phosphate-buffered saline |
| P. aeruginosa | = | Pseudomonas aeruginosa |
| SDS-PAGE | = | sodium dodecyl sulfate polyacrylamide gel electrophoresis |
| W/D weight ratios | = | wet to dry weight ratios |
Disclosure of potential conflicts of interest
With regard to the content of the manuscript, Teiji Sawa received a patent fee from the Regent of the University of California, USA.
Author contributions
TS designed, coordinated and supervised the research. PL, ET, AT developed the economic model and carried out the economic analysis. HY, MK collected clinical samples and analyzed epidemiological data. MK, HK, MS, SH, YN carried out the animal experiments and biological assays. KM assisted the serum titer measurement. TS and MK wrote the manuscript. All authors revised the manuscript and contributed to improving the paper; all authors read and approved the final manuscript.
Funding
This work was supported by the Japan Society for the Promotion of Science, Grant-in-Aid for Scientific Research (KAKENHI No. 24390403, No. 26670791, and No. 15H05008) and from The Ministry of Education, Culture, Sports, Science and Technology, Japan to Teiji Sawa.