Bacteriophage lambda is a highly stable DNA vaccine delivery vehicle

Abstract

The stability of whole bacteriophage lambda particles, used as a DNA vaccine delivery system has been examined. Phage were found to be highly stable under normal storage conditions. In liquid suspension, no decrease in titre was observed over a 6-month period at 4 and -70 degrees C, and phage stability was unaffected by freeze/thawing. The measured half life of phage in suspension was 36 days at 20 degrees C, 3.4 days at 37 degrees C and 2.3 days at 42 degrees C. Freeze drying of a phage suspension (with or without the stabilizers dry skim milk or trehalose) resulted in 5-20% residual viability. Following desiccation (with or without stabilizers), measured half lives ranged from 20 to 100 days at 20 degrees C, 2.6 to 38 days at 37 degrees C, 2.1 to 26 days at 42 degrees C, 7 to 33 h at 70 degrees C, and 1.3 to 6m at 100 degrees C. In all cases the addition of trehalose significantly increased the stability of the desiccated phage. When stored at -70 degrees C, desiccated phage appeared to be stable in the absence of stabilizers. When phage lambda was diluted into water, a marginal loss in titre was observed over a 2-week period. Over a 24 h period, liquid phage suspensions were stable within the pH range pH 3-11, therefore oral administration of bacteriophage DNA vaccines via drinking water may be possible.