Bhangde Shashank, Fresnay-Murray Stephanie, Garretson Tyler, Ashraf Asma, O'Hagan Derek T, Amiji Mansoor M, Lodaya Rushit N
Department of Pharmaceutical Sciences, School of Pharmacy and Pharmaceutical Sciences, Bouvé College of Health Sciences, Northeastern University, Boston, MA 02115, USA.
GSK, Rockville Centre for Vaccines Research, Rockville, MD 20850, USA.
Vaccines (Basel). 2024 Nov 28;12(12):1343. doi: 10.3390/vaccines12121343.
Adjuvants play a crucial role in improving the immunogenicity of various antigens in vaccines. Squalene-in-water emulsions are clinically established vaccine adjuvants that improve immune responses, particularly during a pandemic. Current manufacturing processes for these emulsion adjuvants include microfluidizers and homogenizers and these processes have been used to produce emulsion adjuvants to meet global demands during a pandemic. These processes, however, are complex and expensive and may not meet the global needs based on the growing populations in low- and middle-income countries. At the forefront of adjuvant research, there is a pressing need to manufacture emulsion adjuvants using novel approaches that balance efficacy, scalability, speed of production, and cost-effectiveness.
In this study, we explored the feasibility of a microfluidic chip platform to address these challenges and evaluated the adjuvanticity of the emulsion adjuvant prepared using the microfluidic chip process in CB6F1 mice model, and compared it with a control formulation. We developed and optimized the process parameters to produce emulsion adjuvants with characteristics similar to SEA160 (control formulation).
The resulting emulsion prepared using the microfluidic chip process (MC160) when mixed with ovalbumin, maintained antigen structural integrity. Immunogenicity studies in a CB6F1 mouse model, with the Cytomegalovirus glycoprotein B (CMV gB) antigen, resulted in humoral responses that were non-inferior between MC160 and SEA160, thereby validating the microfluidic chip approach for manufacturing emulsion adjuvants.
These findings demonstrate a proof of concept for using microfluidic chip platforms for formulating emulsion adjuvants, offering a simpler manufacturing platform that can be deployed to low- and middle-income countries for rapid production, improving adjuvant access and aiding in pandemic preparedness.
佐剂在提高疫苗中各种抗原的免疫原性方面起着关键作用。水包角鲨烷乳液是临床上已确立的疫苗佐剂，可改善免疫反应，尤其是在大流行期间。这些乳液佐剂的当前制造工艺包括微流控器和匀化器，并且这些工艺已用于生产乳液佐剂以满足大流行期间的全球需求。然而，这些工艺复杂且昂贵，基于低收入和中等收入国家不断增长的人口，可能无法满足全球需求。在佐剂研究的前沿，迫切需要采用新颖的方法来制造乳液佐剂，以平衡功效、可扩展性、生产速度和成本效益。
在本研究中，我们探讨了微流控芯片平台应对这些挑战的可行性，并在CB6F1小鼠模型中评估了使用微流控芯片工艺制备的乳液佐剂的佐剂性，并将其与对照制剂进行比较。我们开发并优化了工艺参数，以生产具有与SEA160（对照制剂）相似特性的乳液佐剂。
使用微流控芯片工艺（MC160）制备的所得乳液与卵清蛋白混合时，保持了抗原结构完整性。在CB6F1小鼠模型中用巨细胞病毒糖蛋白B（CMV gB）抗原进行的免疫原性研究导致MC160和SEA160之间的体液反应无差异，从而验证了微流控芯片方法用于制造乳液佐剂。
这些发现证明了使用微流控芯片平台配制乳液佐剂的概念验证，提供了一个更简单的制造平台，可部署到低收入和中等收入国家进行快速生产，改善佐剂的可及性并有助于大流行防范。
Zotero 插件
