Mariner Jeffrey C, Gachanja James, Tindih Sheltone H, Toye Philip
International Livestock Research Institute, P.O. Box 30709, 00100 Nairobi, Kenya.
International Livestock Research Institute, P.O. Box 30709, 00100 Nairobi, Kenya.
Vaccine. 2017 Jun 27;35(30):3773-3779. doi: 10.1016/j.vaccine.2017.05.040. Epub 2017 May 29.
The research objective was to develop a thermostable vaccine against peste des petits ruminants (PPR), a morbilliviral disease of small ruminants targeted for eradication that is a major constraint on the livelihoods of the rural poor throughout much of Africa and Asia. Although existing PPR vaccines provide life-long immunity, they require continuous refrigeration. This limits their utility in developing countries. Methods for the lyophilization of a related morbillivirus, rinderpest (RP), resulted in vaccine that could be used in the field for up to 30days without refrigeration which was a major contribution to the global eradication of RP completed in 2011. The present research applied the rinderpest lyophilization method to the attenuated Nigeria 75/1 PPR vaccine strain, and measured thermostability in accelerated stability tests (AST) at 37°C. The shelf-life of the vaccine was determined as the time a vial retained the minimum dose required as a 25-dose presentation at the specified temperature. A lactalbumin hydrolysate and sucrose (LS) stabilizer was compared to stabilizers based on trehalose. PPR vaccine produced using the Xerovac drying method was compared to vaccine produced using the rinderpest lyophilization method in AST. LS vaccine was evaluated in AST at 37, 45 and 56°C and an Arrhenius plot was constructed for estimation of stability at temperatures not tested. Vaccines produced using LS and the rinderpest method of lyophilization were the most stable. The shelf-life of the Xerovac preparation was 22.2days at 37°C. The three LS vaccine batches had shelf-lives at 37°C of 177.6, 105.0 and 148.9days, respectively, at 37°C. At 56°C, the shelf-life was 13.7days. The projected half-life at 25°C was 1.3years. This is sufficient thermostability for use without a cold chain for up to 30days which will greatly facilitate the delivery of vaccination in the global eradication of PPR.
研究目标是研发一种针对小反刍兽疫(PPR)的耐热疫苗。小反刍兽疫是一种小反刍动物的麻疹病毒病,是非洲和亚洲大部分地区农村贫困人口生计的主要制约因素,该病目标是要根除。尽管现有的PPR疫苗可提供终身免疫,但它们需要持续冷藏。这限制了它们在发展中国家的实用性。对一种相关麻疹病毒——牛瘟(RP)进行冻干的方法,产生了可在野外使用长达30天而无需冷藏的疫苗,这对2011年完成的全球根除牛瘟工作做出了重大贡献。本研究将牛瘟冻干方法应用于减毒的尼日利亚75/1 PPR疫苗株,并在37℃的加速稳定性试验(AST)中测量其热稳定性。疫苗的保质期被确定为在指定温度下一个小瓶保留作为25剂量呈现所需的最小剂量的时间。将乳白蛋白水解物和蔗糖(LS)稳定剂与基于海藻糖的稳定剂进行比较。在AST中,将使用Xerovac干燥方法生产的PPR疫苗与使用牛瘟冻干方法生产的疫苗进行比较。对LS疫苗在37、45和56℃的AST中进行评估,并构建阿累尼乌斯图以估计未测试温度下的稳定性。使用LS和牛瘟冻干方法生产的疫苗最稳定。Xerovac制剂在37℃的保质期为22.2天。三批LS疫苗在37℃的保质期分别为177.6、105.0和148.9天。在56℃时,保质期为13.7天。预计在25℃的半衰期为1.3年。这种热稳定性足以在无冷链的情况下使用长达30天,这将极大地促进在全球根除PPR过程中的疫苗接种工作。