Tunable degradation of acetalated dextran microparticles enables controlled vaccine adjuvant and antigen delivery to modulate adaptive immune responses

Abstract

Subunit vaccines are often poorly immunogenic, and adjuvants and/or delivery vehicles, such as polymeric microparticles (MPs), can be used to enhance immune responses. MPs can also be used to understand cell activation kinetics and the significant impact antigen and adjuvant release has on adaptive immune responses. By controlling antigen and adjuvant release, we can determine if it is important to have precise temporal control over release of these elements to optimize the peak and duration of protective immunity and improve vaccine safety profiles. In order to study the effect of tunable adjuvant or antigen delivery on generation of adaptive immunity, we used acetalated dextran (Ace-DEX) MPs. Ace-DEX MPs were used because their tunable degradation can be controlled based on polymer cyclic acetal coverage (CAC). Ace-DEX MPs of varying degradation profiles were used to deliver murabutide or ovalbumin (OVA) as a model adjuvant or antigen, respectively. When murabutide was encapsulated within Ace-DEX MPs to test for controlled adjuvant delivery, fast-degrading MPs exhibited higher humoral and cellular responses in vivo at earlier time points, while slow-degrading MPs resulted in stronger responses at later time points. When OVA was encapsulated within Ace-DEX MPs to test for controlled antigen delivery, fast-degrading MPs induced greater antibody and cytokine production throughout the length of the experiment. This differential response suggests the need for distinct, flexible control over adjuvant or antigen delivery and its impact on immune response modulation.

Carbohydrate Conjugates in Vaccine Developments

“…The in vivo study indicated that delivering PA and adjuvant in separate particles may provide a faster and stronger immune response toward anthrax. This finding supported the idea that adjuvant and antigen should be encapsulated in separate Ac-Dex particles optimized for each component with different CAC percentages (Chen et al, 2018b).…”

“…The difference might be attributed to the surface chemistry difference of the two materials due to the different degradation rate. A recent in vivo study (Chen et al, 2018b) showed that OVA loaded Ac-Dex particles with 20% cyclic acetal coverage (CAC) generated stronger antibody response during the entire experiment period compared to particles with 40 and 60% CAC. Notably, when the particles were used for adjuvant delivery, the immune activating behavior was different.…”

Fabrication of Polymeric Microparticles by Electrospray: The Impact of Experimental Parameters

“…This section will cover the electric field parameter and its impact on ES technology and on the generated MPs. The ES process only starts when a voltage is applied [10], depending on the formulations, the voltage can vary from 2.5 to 30 kV [15,31,41,57,58]. Correia et al investigated the effect of the electric field on designing PVDF MPs.…”

“…This is influenced by the distance between the tip of the needle and the collector, and this distance influences the properties of the MPs, such as size and evaporation rate of the solvent [30,59]. Here, the distance between the tip of the needle and the collector can be adjusted from 6 to 30 cm [28,29,31,36,57,[60][61][62]. In this context, Faramarzi et al observed that when designing PLGA MPs at distances of 4, 7, 13, 19, and 26 cm, as the distance increases to values greater than 13 cm, the size of the MPs decreased slightly to a diameter of 3.6 µm [39].…”

Disease‐Triggered Drug Release Effectively Prevents Acute Inflammatory Flare‐Ups, Achieving Reduced Dosing

“…Measuring pH‐fluctuations noninvasively would certainly aid in the design of disease‐triggered drug release, and highly sensitive probes are being developed . Expanding the versatility of the particles and tailor them to the desired disease could include tuning the degree of acetalation and particle size to better suit the desired pH‐range, where the tuned release kinetics and stability could extend the prophylactic capacity of the particles …”