Formulation Design, Optimization and In Vivo Evaluations of an α-Tocopherol-Containing Self-Emulsified Adjuvant System using Inactivated Influenza Vaccine
Formulation Design, Optimization and In Vivo Evaluations of an α-Tocopherol-Containing Self-Emulsified Adjuvant System using Inactivated Influenza Vaccine
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DOI：
10.1016/j.jconrel.2019.10.042
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发表时间：
2019-12-28
影响因子：
10.8
通讯作者：
O'Hagan, Derek T.
中科院分区：
文献类型：
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作者：
Lodaya, Rushit N.;Kanitkar, Amey P.;O'Hagan, Derek T.
α-生育酚已被用作人类的免疫补充剂、几种兽用疫苗中的乳剂佐剂组分以及AS 03的免疫调节组分，AS 03是一种用于H1N1大流行疫苗（Pandemrix）的乳剂佐剂。AS 03采用微流化和高压均质化生产。这种高能量和复杂的制造工艺使得大规模生产乳液佐剂变得困难和昂贵，特别是在发展中国家。在这项研究中，我们探索了更简单，相对便宜的方法，制定含有α-生育酚的乳液佐剂，有可能在任何完善的规模扩大设施。这可能有助于生产和储存佐剂剂量，从而有助于大流行的准备。我们使用实验设计作为工具，探索将α-生育酚掺入含有角鲨烯油和聚山梨酯80的自乳化系统中。我们创建了新的自乳化佐剂系统（SE-AS），并在BALB/c小鼠体内与灭活四价流感疫苗（QIV）一起评估其效力，并测试针对四种疫苗株的细胞和体液免疫应答。
alpha-Tocopherol has been used as an immune supplement in humans, as an emulsion adjuvant component in several veterinary vaccines as well as an immunomodulatory component of AS03, an emulsion adjuvant that was used in an H1N1 pandemic vaccine (Pandemrix). AS03 is manufactured using microfluidization and high-pressure homogenization. Such high energy and complex manufacturing processes make it difficult and expensive to produce emulsion adjuvants on a large scale, especially in developing countries. In this study we have explored simpler, comparatively inexpensive methods, to formulate emulsion adjuvants containing alpha-tocopherol, that have the potential to be made in any well-established scale-up facility. This might facilitate producing and stock-piling adjuvant doses and therefore aide in pandemic preparedness. We used design of experiment as a tool to explore incorporating alpha-tocopherol into self-emulsified systems containing squalene oil and polysorbate 80. We created novel self-emulsified adjuvant systems (SE-AS) and evaluated their potency in vivo in BALB/c mice with inactivated quadrivalent influenza vaccine (QIV) and tested the cellular and humoral immune responses against the four vaccine strains.