Polyesters (e.g. poly(lactic-co-glycolic acid) (PLGA), polycaptolactone (PCL), some polyanhydrides) often have degradation rates on the order of months, in addition to acidic degradation byproducts. This contrasts with Ac-DEX that has tunable degradation rates that can range from hours to months and degrades into benign levels of dextran, acetone and ethanol. The cyclic and acyclic acetals that comprise Ac-DEX have different rates of hydrolysis. The more cyclic acetals that cover dextran’s hydroxyl groups, the slower the polymer degrades. Therefore, cyclic acetal coverage (CAC) is used to relate the degradation rate of Ac-DEX. At pH 5 (where Ac-DEX degradation ~2 logs faster than at neutral pH) degradation half-lives of Ac-DEX MPs equal: 20% CAC (0.25 hr), 40% CAC (2.9 hr), 60% CAC (21.3 hr).1-3Using this dynamic range, we formulated microparticles into a universal influenza vaccine and illustrated a dependence on tunability with regards to antibody production, cellular response, and protection against a lethal challenge. Ac-DEX was reacted and characterized as previously reported. Ac-DEX microparticles (MPs) were formed via emulsion and loaded with cGAMP and/or M2e. When mice were vaccinated subcutaneously at day 0 and 21 with Ac-DEX MPs of various CAC, they displayed a variable total serum IgG, isotype, and cellular responses. Moreover, when challenged with influenza at day 56, protection was significantly different depending on the degradation rate used to encapsulate M2e. Peak responses occurred at different CACs than observed with other antigens and adjuvants, indicating different antigens and adjuvants require formulation in MPs of different degradation rates. Here we illustrate the utility of Ac-DEX’s degradation tunability for vaccine delivery applications, in that fine tuning of rate has dramatic effect on formulation efficacy.
Summarize how vaccine element release rate effect the efficacy and immune response of particulate vaccine.
Relate what elements of particle fabrication can denature proteins when making vaccine formulations.