Detecting and preventing reversion to toxicity for a formaldehyde-treated C. difficile toxin B mutant

Highlights • A C. difficile toxin B mutant with five mutations (mTcdB) has residual toxicity. • Formaldehyde can remove residual toxicity but reversion in liquid can occur. • In-vivo mouse toxicity and biochemical assays are sensitive indicators of reversion. • Lyophilization after formaldehyde remo...

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Veröffentlicht in:	Vaccine 2015-01, Vol.33 (1), p.252-259
Hauptverfasser:	Wang, Bei, Wang, Su, Rustandi, Richard R, Wang, Feng, Mensch, Christopher D, Hong, Laura, Kristopeit, Adam, Secore, Susan, Dornadula, Geethanjali, Kanavage, Anthony, Heinrichs, Jon H, Mach, Henryk, Blue, Jeffrey T, Thiriot, David S
Format:	Artikel
Sprache:	eng
Schlagworte:	Allergy and Immunology Animals Bacterial Proteins - chemistry Bacterial Proteins - immunology Bacterial Proteins - toxicity Bacterial Toxins - chemistry Bacterial Toxins - immunology Bacterial Toxins - toxicity Bacterial Vaccines - chemistry Bacterial Vaccines - immunology Bacterial Vaccines - radiation effects Bacterial Vaccines - toxicity Chromatography, Ion Exchange Clostridium difficile Clostridium difficile toxin B Drug Storage Electrophoresis, Polyacrylamide Gel Female Formaldehyde - metabolism Freeze Drying Mice, Inbred C57BL Mutant Proteins - chemistry Mutant Proteins - immunology Mutant Proteins - toxicity Temperature Time Factors Toxoid vaccines Toxoids - chemistry Toxoids - immunology Toxoids - toxicity
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Beschreibung
Zusammenfassung:	Highlights • A C. difficile toxin B mutant with five mutations (mTcdB) has residual toxicity. • Formaldehyde can remove residual toxicity but reversion in liquid can occur. • In-vivo mouse toxicity and biochemical assays are sensitive indicators of reversion. • Lyophilization after formaldehyde removal prevents mTcdB reversion to toxicity. • Including formaldehyde can progressively modify mTcdB in the lyophilized state.
ISSN:	0264-410X 1873-2518
DOI:	10.1016/j.vaccine.2014.06.032