PDF(Pubmed)
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：
采用设计者抗原如计算优化的广义反应性抗原(COBRA)血凝素(HA)的亚单位疫苗具有将免疫应答引向流感病毒上更有效和广泛中和靶标的潜力。然而,亚单位疫苗通常需要与佐剂共同施用以引起强烈的免疫反应。一种这样的佐剂是干扰素基因的刺激剂(STING)激动剂环二核苷酸3'3'-环磷酸鸟苷-磷酸腺苷(cGAMP)。我们已经表明,通过电喷雾将cGAMP包封在缩醛化葡聚糖(Ace-DEX)微粒中导致显著更大的生物活性。电喷雾是实现优异的封装效率的连续制造工艺。然而,使用单个喷头的电喷雾的吞吐量是有限的。在这里，我们报告了一种多路电喷雾设备的开发，其吞吐量比单头设备大一个数量级。体外和体内的物理化学表征和佐剂活性的评估表明，用更高通量的方法生产的微粒同样适合用作有效的疫苗佐剂，以诱导对COBRAHA抗原的平衡免疫应答。
