Comparative study of acetalated-dextran microparticle fabrication methods for a clinically translatable subunit-based influenza vaccine.
Comparative study of acetalated-dextran microparticle fabrication methods for a clinically translatable subunit-based influenza vaccine.
复制标题
用于临床可转化的基于亚基的流感疫苗的乙醛化葡聚糖微粒制造方法的比较研究。
DOI：
10.1016/j.ijpharm.2024.123836
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发表时间：
2024
影响因子：
5.8
通讯作者：
Bachelder,EricM
中科院分区：
文献类型：
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作者：
Pena,ErikS;Batty,ColeJ;Hendy,DylanA;Yang,Shuangshuang;Ontiveros-Padilla,Luis;Stiepel,RebecaT;Ting,JennyP-Y;Ainslie,KristyM;Bachelder,EricM
最常见的流感疫苗是用鸡蛋生产的灭活病毒，这是一种耗时的生产方法，由于疫苗毒株与主要流通毒株不匹配，因此效果不同。与传统的鸡蛋疫苗相比，基于亚单位的疫苗生产时间更短，但通常需要使用佐剂来诱导高度保护性的免疫反应。然而，目前FDA批准的流感疫苗佐剂(MF59)引起的主要是辅助性T细胞2型(Th2)偏向的体液免疫反应。能够刺激Th1细胞反应的佐剂与对抗流感的保护作用更强相关。环二核苷酸cGAMP已被证明提供有效的Th1反应，但需要使用递送载体来最好地启动其在胞浆中的信号通路。本论文以缩醛葡聚糖(Ace-DEX)为聚合物，采用复乳法、电喷雾法和喷雾干燥法制备了cGAMP微球。本研究比较了每种制备方法对亲水性佐剂cGAMP的包封率和保留率。我们将它们的治疗效果与类似MF59的佐剂Addavax进行了比较，cGAMP Ace-DEX MPS在接种BALB/c小鼠后提供了更强的Th1反应。此外，我们将Ace-DEX MPS与喷雾干燥的MPS进行了比较，MPS由一种常用的药物传递聚合物聚乳酸-乙醇酸(PLGA)组成。我们观察到，所有Ace-DEX MPS对PLGA MPS都有相似的体液和细胞反应。总体而言，这里显示的结果表明，Ace-DEX作为药物输送的聚合物可以发挥与PLGA相似的作用，喷雾干燥可以提供一种有效的方法来生产MPS来包裹cGAMP并刺激免疫系统。
The most common influenza vaccines are inactivated viruses produced in chicken eggs, which is a time-consuming production method with variable efficacy due to mismatches of the vaccine strains to the dominant circulating strains. Subunit-based vaccines provide faster production times in comparison to the traditional egg-produced vaccines but often require the use of an adjuvant to elicit a highly protective immune response. However, the current FDA approved adjuvant for influenza vaccines (MF59) elicits a primarily helper T-cell type 2 (Th2)-biased humoral immune response. Adjuvants that can stimulate a Th1 cellular response are correlated to have more robust protection against influenza. The cyclic dinucleotide cGAMP has been shown to provide a potent Th1 response but requires the use of a delivery vehicle to best initiate its signalling pathway in the cytosol. Herein, acetalated dextran (Ace-DEX) was used as the polymer to fabricate microparticles (MPs) via double-emulsion, electrospray, and spray drying methods to encapsulate cGAMP. This study compared each fabrication method’s ability to encapsulate and retain the hydrophilic adjuvant cGAMP. We compared their therapeutic efficacy to Addavax, an MF59-like adjuvant, and cGAMP Ace-DEX MPs provided a stronger Th1 response in vaccinated BALB/c mice. Furthermore, we compared Ace-DEX MPs to spray dried MPs composed from a commonly used polymer for drug delivery, poly(lactic-co-glycolic acid) (PLGA). We observed that all Ace-DEX MPs elicited similar humoral and cellular responses to the PLGA MPs. Overall, the results shown here indicate Ace-DEX can perform similarly to PLGA as a polymer for drug delivery and that spray drying can provide an efficient way to produce MPs to encapsulate cGAMP and stimulate the immune system.