Antibody Response is Differentially Influenced by PLGA-PAD4 Particle Characteristics

Abstract

Background: Anthrax, as a zoonotic disease, is considered a major bioterror threat. Development of effective prophylactic approaches is needed to combat this disease. The protective antigen domain 4 (PAD4) has been extensively studied as a vaccine candidate against anthrax. Previously, we showed that PAD4 can be successfully encapsulated in poly (lactide-co-glycolide) (PLGA)-based particulate systems. Objectives: We aimed to determine if there is an intricate relationship between the parameters of PLGA particulate process and the associated immunogenicity. Methods: In this study, PLGA (50:50) and PLGA (85:15) with a similar molecular weight were used as the polymer variants. Polymer variants were evaluated using 3 adaptations of w/o/w solvent evaporation method. Six variants of PLGA-PAD4 particulate systems were developed and studied for size, antigen content, and immunogenicity. Results: NaCl in the external aqueous phase was required to achieve nonporous and spherical microparticles. Particle size was found to be dependent on the applied methods, and there was no significant difference in size by varying the PLGA compositions. PLGA variants showed a differential behavior with antigen encapsulation in the evaluated methods. The hydrophobic particulate vaccine with the mean diameter of ~ 3 µm elicited the highest IgG titer, compared to particles with mean diameters of ~ 0.2 and ~ 7 µm. Conclusions: This study could help determine the composition of novel PAD4-encapsulated PLGA-based vaccine formulations.