Strategies for improved stability of Peste des Petits Ruminants Vaccine

被引:22
|
作者
Silva, Ana Carina [1 ,2 ]
Carrondo, Manuel J. T. [1 ,3 ]
Alves, Paula M. [1 ,2 ]
机构
[1] ITQB UNL, P-2781901 Oeiras, Portugal
[2] IBET, P-2781901 Oeiras, Portugal
[3] FCT UNL, Engn Bioquim Lab, P-2825 Monte De Caparica, Portugal
关键词
Peste des Petits Ruminants Vaccine; Thermostability; Formulation; Medium composition manipulation; Osmolality; HAMSTER OVARY CELLS; RETROVIRAL VECTORS; HYPEROSMOTIC PRESSURE; CHEMICAL STABILIZERS; GENE-THERAPY; PPR VACCINE; VIRUS; FRUCTOSE; CULTURE; THERMOSTABILITY;
D O I
10.1016/j.vaccine.2011.04.102
中图分类号
R392 [医学免疫学]; Q939.91 [免疫学];
学科分类号
100102 ;
摘要
The main focus of this work was the improvement of the stability of the current PPRV vaccine. First, new formulations based on the Tris buffer were tested, with and without the addition of sucrose and trehalose and compared with the formulation normally used to stabilize the vaccine, the Weybridge medium. The results show a virus half-life of 21 h at 37 degrees C and 1 month at 4 degrees C for the Tris/trehalose liquid formulation and, in the lyophilized form, the formulation was able to maintain the viral titer above the 1 x 10(4) TCID(50)/mL (>10 doses/mL) for at least 21 months at 4 degrees C (0.6 log lost), 144 h at 37 degrees C (0.6 log lost) and 120 h at 45 degrees C (1 log lost). Secondly, a strategy based on culture medium composition manipulation aiming at improving the intrinsic PPRV vaccine stability was also evaluated. The addition of 25 mM fructose resulted in a higher virus production (1 log increase) with higher stability (2.6-fold increase compared to glucose 25 mM) at 37 degrees C. Increased concentrations of NaCl, improved virus release, reducing the cell-associated fraction of the virus produced. Moreover this harvesting strategy is scalable and more suitable for a larger scale production than the freeze/thaw cycles normally used. The information gathered in this work showed that it is possible for the PPRV vaccine to have adequate short-term stability at non-freezing temperatures to support manufacturing, short-term shipping and storage. The identification of a more stable formulation should significantly enhance the utility of the vaccine in the control of a PPRV outbreak. (C) 2011 Elsevier Ltd. All rights reserved.
引用
收藏
页码:4983 / 4991
页数:9
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