Development of a Freeze-Dried, Heat-Stable Influenza Subunit Vaccine Formulation
Development of a Freeze-Dried, Heat-Stable Influenza Subunit Vaccine Formulation
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DOI：
10.1371/journal.pone.0164692
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发表时间：
2016-11-16
期刊：
影响因子：
3.7
通讯作者：
Chen, Dexiang
中科院分区：
文献类型：
--
作者：
Flood, Alexander;Estrada, Marcus;Chen, Dexiang
流感大流行仍然是一个重大的公共卫生问题。预防大流行的一项关键战略是储存和预先放置稳定的流感疫苗，以便在疫情爆发时迅速部署。然而，目前大多数流感疫苗的配方为液体，仅在2摄氏度至8摄氏度的温度范围内稳定，并且需要使用冷链，这使得疫苗的运输、分发和储存变得复杂和昂贵，特别是对发展中国家而言。为了支持美国和国际上的大流行性流感防范国家战略，我们利用冷冻干燥技术开发了两种稳定型H1N1流感亚单位疫苗的先导干燥配方。稳定制剂除了含有表面活性剂和磷酸盐缓冲液外，还含有二糖如蔗糖或海藻糖和甘氨酸的赋形剂组合。冻干疫苗在小鼠体内研究中显示是安全的，并保持免疫原性。此外，在25摄氏度和37摄氏度的储存温度下，铅制剂在40个月后没有表现出明显的活性损失。这种稳定性尤其具有吸引力，因为它可以消除使用冷链进行疫苗部署的需要，并在适当情况下促进疫苗分发与一般药物分发的整合。这些冷冻干燥的耐热流感亚单位疫苗还可以减少疫苗储存周转的频率，为大流行防范提供了一种具有成本效益的选择。
An influenza pandemic remains a major public health concern. A key strategy to prevent a pandemic is to stockpile and pre-position stable influenza vaccine to allow rapid deployment in response to an outbreak. However, most influenza vaccines today are formulated as liquids that are stable only within a temperature range of 2 degrees C to 8 degrees C and require use of a cold chain, making vaccine transportation, distribution, and storage complicated and expensive, particularly for developing countries. To support the National Strategy for Pandemic Influenza preparedness in the United States and internationally, we developed two lead dry formulations of stable H1N1 influenza subunit vaccines using freeze-drying technology. The stable formulations contain an excipient combination of a disaccharide, such as sucrose or trehalose, and glycine, in addition to a surfactant and phosphate buffer. The freeze-dried vaccines were shown to be safe and remained immunogenic in an in vivo study in mice. Moreover, the lead formulations demonstrated no significant loss of activity after 40 months at storage temperatures of 25 degrees C and 37 degrees C. This stability can be particularly attractive as it could eliminate the need to use a cold chain for vaccine deployment and facilitate integration of vaccine distribution with general drug distribution where appropriate. These freeze-dried thermostable influenza subunit vaccines could also reduce the frequency of vaccine stockpile turnover, offering a cost-effective option for pandemic preparedness.