期刊
INTERNATIONAL JOURNAL OF PHARMACEUTICS
卷 622, 期 -, 页码 -出版社
ELSEVIER
DOI: 10.1016/j.ijpharm.2022.121839
关键词
Vaccine manufacturing; Vaccine adjuvant; STING; Flu; COBRA; Microparticle
资金
- National Science Foundation [ECCS-2025064]
- Cancer Center Core Support Grant [2017-IDG-1025]
- North Carolina Biotech Center [P30 CA016086]
- National Institutes of Health [1UM2AI30836-01]
- NIH NIAID [R01AI147497, R01AI141333, R41AI140795]
- Collaborative Influenza Vaccine Innovation Centers (CIVICs) [75N93019C00052]
This study reports a new method of encapsulating an interferon gene stimulator using electrospray, which significantly improves its biological activity. A multiplexed electrospray apparatus with higher throughput than a single-head apparatus was also developed. In vitro and in vivo experiments demonstrated that microparticles produced using this high throughput process are an effective vaccine adjuvant to induce a balanced immune response.
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.
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