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

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.

Automated summary

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.