4.7 Article

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

Journal

INTERNATIONAL JOURNAL OF PHARMACEUTICS
Volume 622, Issue -, Pages -

Publisher

ELSEVIER
DOI: 10.1016/j.ijpharm.2022.121839

Keywords

Vaccine manufacturing; Vaccine adjuvant; STING; Flu; COBRA; Microparticle

Funding

  1. National Science Foundation [ECCS-2025064]
  2. Cancer Center Core Support Grant [2017-IDG-1025]
  3. North Carolina Biotech Center [P30 CA016086]
  4. National Institutes of Health [1UM2AI30836-01]
  5. NIH NIAID [R01AI147497, R01AI141333, R41AI140795]
  6. Collaborative Influenza Vaccine Innovation Centers (CIVICs) [75N93019C00052]

Ask authors/readers for more resources

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.

Authors

I am an author on this paper
Click your name to claim this paper and add it to your profile.

Reviews

Primary Rating

4.7
Not enough ratings

Secondary Ratings

Novelty
-
Significance
-
Scientific rigor
-
Rate this paper

Recommended

No Data Available
No Data Available