Quality-Controlled Small-Scale Production of a Well-Defined Bacteriophage Cocktail for Use in Human Clinical Trials

被引：350

作者：

Merabishvili, Maya ^{[1
,2
,8
]}

Pirnay, Jean-Paul ^{[2
]}

Verbeken, Gilbert ^{[2
]}

Chanishvili, Nina ^{[1
]}

Tediashvili, Marina ^{[1
]}

Lashkhi, Nino ^{[1
]}

Glonti, Thea ^{[1
]}

Krylov, Victor ^{[3
]}

Mast, Jan ^{[4
]}

Van Parys, Luc ^{[5
]}

Lavigne, Rob ^{[6
]}

Volckaert, Guido ^{[6
]}

Mattheus, Wesley ^{[6
]}

Verween, Gunther ^{[2
]}

De Corte, Peter ^{[2
]}

Rose, Thomas ^{[2
]}

Jennes, Serge ^{[2
]}

Zizi, Martin ^{[5
,7
]}

De Vos, Daniel ^{[2
]}

Vaneechoutte, Mario ^{[8
]}

机构：

[1] EIBMV, Tbilisi, Georgia

[2] Queen Astrid Mil Hosp, Burn Ctr, LabMCT, Brussels, Belgium

[3] SIGSIM, Lab Bacteriophage Genet, Moscow, Russia

[4] VAR, Unit Electron Microscopy, Brussels, Belgium

[5] Queen Astrid Mil Hosp, Sect Hlth Div WellBeing, Brussels, Belgium

[6] Katholieke Univ Leuven, LoGT, Louvain, Belgium

[7] Free Univ Brussels, Dept Physiol, B-1050 Brussels, Belgium

[8] Ghent Univ Hosp, LBR, Ghent, Belgium

来源：

PLOS ONE | 2009年 / 4卷 / 03期

关键词：

ESCHERICHIA-COLI DIARRHEA; PSEUDOMONAS-AERUGINOSA; GENOMIC ANALYSIS; PHI-KMV; PHAGE; THERAPY; MICE; INFECTIONS; EFFICACY; CALVES;

D O I：

10.1371/journal.pone.0004944

中图分类号：

O [数理科学和化学]; P [天文学、地球科学]; Q [生物科学]; N [自然科学总论];

学科分类号：

07 ; 0710 ; 09 ;

摘要：

We describe the small-scale, laboratory-based, production and quality control of a cocktail, consisting of exclusively lytic bacteriophages, designed for the treatment of Pseudomonas aeruginosa and Staphylococcus aureus infections in burn wound patients. Based on succesive selection rounds three bacteriophages were retained from an initial pool of 82 P. aeruginosa and 8 S. aureus bacteriophages, specific for prevalent P. aeruginosa and S. aureus strains in the Burn Centre of the Queen Astrid Military Hospital in Brussels, Belgium. This cocktail, consisting of P. aeruginosa phages 14/1 (Myoviridae) and PNM (Podoviridae) and S. aureus phage ISP (Myoviridae) was produced and purified of endotoxin. Quality control included Stability (shelf life), determination of pyrogenicity, sterility and cytotoxicity, confirmation of the absence of temperate bacteriophages and transmission electron microscopy-based confirmation of the presence of the expected virion morphologic particles as well as of their specific interaction with the target bacteria. Bacteriophage genome and proteome analysis confirmed the lytic nature of the bacteriophages, the absence of toxin-coding genes and showed that the selected phages 14/1, PNM and ISP are close relatives of respectively F8, phi KMV and phage G1. The bacteriophage cocktail is currently being evaluated in a pilot clinical study cleared by a leading Medical Ethical Committee.

引用

页数：10

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