Evaluation of the Stability of Bacteriophages in Different Solutions Suitable for the Production of Magistral Preparations in Belgium

In Belgium, the incorporation of phages into magistral preparations for human application has been permitted since 2018. The stability of such preparations is of high importance to guarantee quality and efficacy throughout treatments. We evaluated the ability to preserve infectivity of four differen...

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Main Authors: Hans Duyvejonck, Maya Merabishvili, Mario Vaneechoutte, Steven de Soir, Rosanna Wright, Ville-Petri Friman, Gilbert Verbeken, Daniel De Vos, Jean-Paul Pirnay, Els Van Mechelen, Stefan J. T. Vermeulen
Format: Article
Language:English
Published: MDPI AG 2021-05-01
Series:Viruses
Subjects:
Online Access:https://www.mdpi.com/1999-4915/13/5/865
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author Hans Duyvejonck
Maya Merabishvili
Mario Vaneechoutte
Steven de Soir
Rosanna Wright
Ville-Petri Friman
Gilbert Verbeken
Daniel De Vos
Jean-Paul Pirnay
Els Van Mechelen
Stefan J. T. Vermeulen
author_facet Hans Duyvejonck
Maya Merabishvili
Mario Vaneechoutte
Steven de Soir
Rosanna Wright
Ville-Petri Friman
Gilbert Verbeken
Daniel De Vos
Jean-Paul Pirnay
Els Van Mechelen
Stefan J. T. Vermeulen
author_sort Hans Duyvejonck
collection DOAJ
description In Belgium, the incorporation of phages into magistral preparations for human application has been permitted since 2018. The stability of such preparations is of high importance to guarantee quality and efficacy throughout treatments. We evaluated the ability to preserve infectivity of four different phages active against three different bacterial species in five different buffer and infusion solutions commonly used in medicine and biotechnological manufacturing processes, at two different concentrations (9 and 7 log pfu/mL), stored at 4 °C. DPBS without Ca<sup>2+</sup> and Mg<sup>2+</sup> was found to be the best option, compared to the other solutions. Suspensions with phage concentrations of 7 log pfu/mL were unsuited as their activity dropped below the effective therapeutic dose (6–9 log pfu/mL), even after one week of storage at 4 °C. Strong variability between phages was observed, with <i>Acinetobacter baumannii</i> phage Acibel004 being stable in four out of five different solutions. We also studied the long term storage of lyophilized staphylococcal phage ISP, and found that the titer could be preserved during a period of almost 8 years when sucrose and trehalose were used as stabilizers. After rehydration of the lyophilized ISP phage in saline, the phage solutions remained stable at 4 °C during a period of 126 days.
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spelling doaj.art-d6db5cbf7d9e489a9d87983fecf346332023-11-21T18:49:52ZengMDPI AGViruses1999-49152021-05-0113586510.3390/v13050865Evaluation of the Stability of Bacteriophages in Different Solutions Suitable for the Production of Magistral Preparations in BelgiumHans Duyvejonck0Maya Merabishvili1Mario Vaneechoutte2Steven de Soir3Rosanna Wright4Ville-Petri Friman5Gilbert Verbeken6Daniel De Vos7Jean-Paul Pirnay8Els Van Mechelen9Stefan J. T. Vermeulen10Research Center Health & Water Technology, University College Ghent, Keramiekstraat 80, B-9000 Gent, BelgiumLaboratory Bacteriology Research, Faculty of Medicine & Health Sciences, Ghent University, C. Heymanslaan 10, B-9000 Gent, BelgiumLaboratory Bacteriology Research, Faculty of Medicine & Health Sciences, Ghent University, C. Heymanslaan 10, B-9000 Gent, BelgiumLaboratory for Molecular and Cellular Technology, Queen Astrid Military Hospital, Bruynstraat 1, 1120 Brussel, BelgiumDepartment of Biology, University of York, Wentworth Way, York YO10 5DD, UKDepartment of Biology, University of York, Wentworth Way, York YO10 5DD, UKLaboratory for Molecular and Cellular Technology, Queen Astrid Military Hospital, Bruynstraat 1, 1120 Brussel, BelgiumLaboratory for Molecular and Cellular Technology, Queen Astrid Military Hospital, Bruynstraat 1, 1120 Brussel, BelgiumLaboratory for Molecular and Cellular Technology, Queen Astrid Military Hospital, Bruynstraat 1, 1120 Brussel, BelgiumResearch Center Health & Water Technology, University College Ghent, Keramiekstraat 80, B-9000 Gent, BelgiumResearch Center Health & Water Technology, University College Ghent, Keramiekstraat 80, B-9000 Gent, BelgiumIn Belgium, the incorporation of phages into magistral preparations for human application has been permitted since 2018. The stability of such preparations is of high importance to guarantee quality and efficacy throughout treatments. We evaluated the ability to preserve infectivity of four different phages active against three different bacterial species in five different buffer and infusion solutions commonly used in medicine and biotechnological manufacturing processes, at two different concentrations (9 and 7 log pfu/mL), stored at 4 °C. DPBS without Ca<sup>2+</sup> and Mg<sup>2+</sup> was found to be the best option, compared to the other solutions. Suspensions with phage concentrations of 7 log pfu/mL were unsuited as their activity dropped below the effective therapeutic dose (6–9 log pfu/mL), even after one week of storage at 4 °C. Strong variability between phages was observed, with <i>Acinetobacter baumannii</i> phage Acibel004 being stable in four out of five different solutions. We also studied the long term storage of lyophilized staphylococcal phage ISP, and found that the titer could be preserved during a period of almost 8 years when sucrose and trehalose were used as stabilizers. After rehydration of the lyophilized ISP phage in saline, the phage solutions remained stable at 4 °C during a period of 126 days.https://www.mdpi.com/1999-4915/13/5/865phageAPImagistral preparationbuffersinfusion solutionsinfectivity
spellingShingle Hans Duyvejonck
Maya Merabishvili
Mario Vaneechoutte
Steven de Soir
Rosanna Wright
Ville-Petri Friman
Gilbert Verbeken
Daniel De Vos
Jean-Paul Pirnay
Els Van Mechelen
Stefan J. T. Vermeulen
Evaluation of the Stability of Bacteriophages in Different Solutions Suitable for the Production of Magistral Preparations in Belgium
Viruses
phage
API
magistral preparation
buffers
infusion solutions
infectivity
title Evaluation of the Stability of Bacteriophages in Different Solutions Suitable for the Production of Magistral Preparations in Belgium
title_full Evaluation of the Stability of Bacteriophages in Different Solutions Suitable for the Production of Magistral Preparations in Belgium
title_fullStr Evaluation of the Stability of Bacteriophages in Different Solutions Suitable for the Production of Magistral Preparations in Belgium
title_full_unstemmed Evaluation of the Stability of Bacteriophages in Different Solutions Suitable for the Production of Magistral Preparations in Belgium
title_short Evaluation of the Stability of Bacteriophages in Different Solutions Suitable for the Production of Magistral Preparations in Belgium
title_sort evaluation of the stability of bacteriophages in different solutions suitable for the production of magistral preparations in belgium
topic phage
API
magistral preparation
buffers
infusion solutions
infectivity
url https://www.mdpi.com/1999-4915/13/5/865
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