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多重电喷雾使 cGAMP 微粒能够高通量生产,作为一种广泛作用的流感疫苗佐剂。

Multiplexed electrospray enables high throughput production of cGAMP microparticles to serve as an adjuvant for a broadly acting influenza vaccine.

机构信息

Division of Pharmacoengineering and Molecular Pharmaceutics, Eshelman School of Pharmacy, University of North Carolina at Chapel Hill, NC, USA.

Immvention Therapeutix, Durham, NC, USA.

出版信息

Int J Pharm. 2022 Jun 25;622:121839. doi: 10.1016/j.ijpharm.2022.121839. Epub 2022 May 24.

Abstract

Subunit vaccines employing designer antigens such as Computationally Optimized Broadly Reactive Antigen (COBRA) hemagglutinin (HA) hold the potential to direct the immune response toward more effective and broadly-neutralizing targets on the Influenza virus. However, subunit vaccines generally require coadministration with an adjuvant to elicit a robust immune response. One such adjuvant is the stimulator of interferon genes (STING) agonist cyclic dinucleotide 3'3'-cyclic guanosine monophosphate-adenosine monophosphate (cGAMP). We have shown that encapsulation of cGAMP in acetalated dextran (Ace-DEX) microparticles through electrospray results in significantly greater biological activity. Electrospray is a continuous manufacturing process which achieves excellent encapsulation efficiency. However, the throughput of electrospray with a single spray head is limited. Here we report the development of a multiplexed electrospray apparatus with an order of magnitude greater throughput than a single-head apparatus. Physicochemical characterization and evaluation of adjuvant activity in vitro and in vivo indicated that microparticles produced with the higher throughput process are equally suited for use as a potent vaccine adjuvant to induce a balanced immune response to COBRA HA antigens.

摘要

使用诸如计算优化的广谱反应性抗原(COBRA)血凝素(HA)等设计抗原的亚单位疫苗有可能将免疫反应引导到流感病毒上更有效和更广泛的中和靶标。然而,亚单位疫苗通常需要与佐剂共同给药以引发强大的免疫反应。一种这样的佐剂是干扰素基因刺激物(STING)激动剂环二核苷酸 3'3'-环鸟苷单磷酸-腺苷单磷酸(cGAMP)。我们已经表明,通过电喷雾将 cGAMP 包封在乙酰化葡聚糖(Ace-DEX)微球中会导致显著更高的生物活性。电喷雾是一种连续制造工艺,可实现出色的封装效率。然而,单个喷头的电喷雾通量有限。在这里,我们报告了一种多路电喷雾装置的开发,其通量比单喷头装置高一个数量级。理化特性表征和体外及体内佐剂活性评估表明,使用更高通量工艺生产的微球同样适合用作有效的疫苗佐剂,以诱导对 COBRA HA 抗原的平衡免疫反应。

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