Jepson Catherine D, March John B
Moredun Research Institute, Pentlands Science Park, Bush Loan, Penicuik EH26 0PZ, Scotland, UK.
Vaccine. 2004 Jun 23;22(19):2413-9. doi: 10.1016/j.vaccine.2003.11.065.
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.
已对用作DNA疫苗递送系统的完整λ噬菌体颗粒的稳定性进行了研究。发现噬菌体在正常储存条件下高度稳定。在液体悬浮液中,在4℃和-70℃下6个月期间未观察到滴度下降,并且噬菌体稳定性不受冻融影响。在20℃下悬浮液中噬菌体的测量半衰期为36天,在37℃下为3.4天,在42℃下为2.3天。噬菌体悬浮液(有或没有稳定剂脱脂奶粉或海藻糖)的冷冻干燥导致5-20%的残余活力。干燥后(有或没有稳定剂),在20℃下测量的半衰期为20至100天,在37℃下为2.6至38天,在42℃下为2.1至26天,在70℃下为7至33小时,在100℃下为1.3至6分钟。在所有情况下,添加海藻糖均显著提高了干燥噬菌体的稳定性。当在-70℃下储存时,干燥的噬菌体在没有稳定剂的情况下似乎是稳定的。当将λ噬菌体稀释到水中时,在2周内观察到滴度略有下降。在24小时期间,液体噬菌体悬浮液在pH 3-11的范围内是稳定的,因此通过饮用水口服噬菌体DNA疫苗可能是可行的。