Characterization of the freeze sensitivity of a hepatitis B vaccine
Characterization of the freeze sensitivity of a hepatitis B vaccine
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DOI：
10.4161/hv.5.1.6494
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发表时间：
2009-01-01
期刊：
影响因子：
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通讯作者：
Braun, LaToya Jones
中科院分区：
文献类型：
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作者：
Chen, Dexiang;Tyagi, Anil;Braun, LaToya Jones
最近的研究表明，含有铝佐剂的疫苗在冷链中暴露于零度以下温度的频率比之前认为的要高。这引起了人们的担忧，即这些冷冻敏感疫苗可能会被损坏并提供不充分的保护。这项研究的目的是描述乙型肝炎疫苗因冷冻暴露而立即发生的质量变化。乙型肝炎疫苗在 0 摄氏度至 -20 摄氏度的冷冻温度下进行最多 3 次试验，持续时间从 1 小时到 7 天不等。分析了疫苗的冰点、粒径分布、三级结构以及体外和体内效力。乙型肝炎疫苗是否冻结取决于一系列因素，包括温度、温度变化率、暴露时间、过冷效应和振动。暴露于“轻度”冷冻（-4 摄氏度或更高）温度的疫苗不会冻结并且质量保持不变。 -10℃或更低温度下的单次或重复冷冻事件与佐剂抗原颗粒的聚集、抗原的结构损伤以及小鼠免疫原性的降低有关。对疫苗的损害随着冷冻时间、较低温度和冷冻次数的增加而增加。随着振动，疫苗在-6℃下1小时后冻结并发生损坏。含有铝盐佐剂的疫苗的冷冻和冷冻损坏对免疫效果构成真正的风险，应通过加强冷链系统或开发冷冻稳定的疫苗制剂来预防。
Recent studies have revealed that vaccines containing aluminum adjuvant are exposed to sub-zero temperatures while in the cold chain more frequently than was previously believed. This raises concerns that these freeze-sensitive vaccines may be damaged and offer inadequate protection. This study was undertaken to characterize the immediate qualitative changes of one such vaccine, hepatitis B, caused by freeze exposure. Hepatitis B vaccine was subjected to freezing temperatures ranging from 0 degrees C to -20 degrees C for up to three episodes with durations ranging from 1 hour to 7 days. The vaccine was analyzed for freezing point, particle size distribution, tertiary structure, and in vitro and in vivo potency. Whether or not hepatitis B vaccine freezes was shown to be dependent on an array of factors including temperature, rate of temperature change, duration of exposure, supercooling effects and vibration. Vaccine exposed to "mild" freezing (-4 degrees C or warmer) temperatures did not freeze and remained qualitatively unaltered. Single or repeated freezing events at temperatures of -10 degrees C or lower were associated with aggregation of the adjuvant-antigen particles, structural damage of the antigen, and reduction of immunogenicity in mice. Damage to the vaccine increased with duration of freezing, lower temperature, and the number of freezing episodes. With vibration, vaccine froze at -6 degrees C after 1 hour and damage occurred. Freezing and freeze damage to vaccines containing aluminum salt adjuvant represent real risks to the effectiveness of immunization and should be prevented by strengthening the cold chain system or, alternatively, development of freeze-stable vaccine formulations.