Infectious Disease Research Institute, Seattle, WA, USA,
Int J Nanomedicine. 2018 Jun 26;13:3689-3711. doi: 10.2147/IJN.S159839. eCollection 2018.
Adjuvants have the potential to increase the efficacy of protein-based vaccines but need to be maintained within specific temperature and storage conditions. Lyophilization can be used to increase the thermostability of protein pharmaceuticals; however, no marketed vaccine that contains an adjuvant is currently lyophilized, and lyophilization of oil-in-water nanoemulsion adjuvants presents a specific challenge. We have previously demonstrated the feasibility of lyophilizing a candidate adjuvanted protein vaccine against (), ID93 + GLA-SE, and the subsequent improvement of thermostability; however, further development is required to prevent physicochemical changes and degradation of the TLR4 agonist glucopyranosyl lipid adjuvant formulated in an oil-in-water nanoemulsion (SE).
In this study, we took a systematic approach to the development of a thermostable product by first identifying compatible solution conditions and stabilizing excipients for both antigen and adjuvant. Next, we applied a design-of-experiments approach to identify stable lyophilized drug product formulations.
We identified specific formulations that contain disaccharide or a combination of disaccharide and mannitol that can achieve substantially improved thermostability and maintain immunogenicity in a mouse model when tested in accelerated and real-time stability studies.
These efforts will aid in the development of a platform formulation for use with other similar vaccines.
佐剂具有提高基于蛋白质的疫苗效力的潜力，但需要在特定的温度和储存条件下保持。冷冻干燥可用于提高蛋白质药物的热稳定性；然而，目前没有含有佐剂的上市疫苗是冷冻干燥的，油包水纳米乳佐剂的冷冻干燥提出了一个特殊的挑战。我们之前已经证明了冻干候选佐剂蛋白疫苗 against （），ID93 + GLA-SE 的可行性，以及随后对热稳定性的改善；然而，需要进一步开发以防止 TLR4 激动剂葡糖苷脂佐剂在油包水纳米乳（SE）中配制的物理化学变化和降解。
在这项研究中，我们首先确定抗原和佐剂的相容溶液条件和稳定赋形剂，采用系统的方法开发热稳定产品。接下来，我们应用实验设计方法来确定稳定的冻干药物产品配方。
我们确定了特定的配方，其中含有二糖或二糖和甘露醇的组合，可以在加速和实时稳定性研究中实现显著提高的热稳定性，并在小鼠模型中保持免疫原性。
这些努力将有助于开发用于其他类似疫苗的平台配方。
