467357 Acetalated Dextran Microparticulate Subunit Anthrax Vaccine Formulated Using Coaxial Electrospray Preserves Toxin Neutralization and Enhances Protection

Tuesday, November 15, 2016: 3:51 PM
Golden Gate 5 (Hilton San Francisco Union Square)
Matthew D. Gallovic1,2, Kevin L. Schully3, Matthew G. Bell3, Margaret A. Elberson3, John R. Palmer3, Christian A. Darko3, Eric M. Bachelder1, Barbara E. Wyslouzil4,5, Andrea M. Keane-Myers3 and Kristy M. Ainslie1, (1)Division of Molecular Pharmaceutics, Eshelman School of Pharmacy, University of North Carolina - Chapel Hill, Chapel Hill, NC, (2)Department of Chemical and Biomolecular Engineering, College of Engineering, The Ohio State University, Columbus, OH, (3)Vaccine and Medical Countermeasures, Biological Defense Research Directorate, Naval Medical Research Center, Fort Detrick, MD, (4)William G. Lowrie Department of Chemical and Biomolecular Engineering, The Ohio State University, Columbus, OH, (5)Department of Chemistry and Biochemistry, The Ohio State University, Columbus, OH

Protein-based subunit vaccines are considered the safest type of vaccine, and their typically poor immunogenicity can be enhanced with well-characterized, potent Th1-skewing adjuvants. The use of polymer particles is an established approach to efficiently deliver both antigens and adjuvants to target antigen-presenting cells. However, particles composed of polyanhydrides and polyesters such as poly(lactic-co-glycolic acid) have detrimental acidic hydrolytic byproducts and relatively slow release kinetics. These substantial drawbacks emphasize the need for new polymer particles that exhibit pH-neutral hydrolytic byproducts and efficient intraphagosomal antigen/adjuvant delivery. Acetalated dextran (Ace-DEX) particles are a novel, acid-degradable formulation that fulfills these preferred design parameters. We have previously demonstrated Ace-DEX particles’ efficacy in several subunit vaccine formulations. These particles were formulated using the common batch solvent evaporation technique, and thus, some of the resultant in vivo immune responses were likely hampered due to the particle fabrication method’s denaturing characteristics.

An alternative polymer particle fabrication method such as coaxial electrohydrodynamic spraying (electrospray) is amenable to overcoming these formulation barriers. Coaxial electrospray processes do not create harsh denaturing conditions and have demonstrated gentle encapsulation of proteins in model studies. Despite these promising results, coaxial electrospray methods have yet to be applied to notable therapeutic or vaccine applications utilizing polymer particles. In our current work, we use coaxial electrospray to formulate an anthrax vaccine. We efficiently and gently encapsulate the labile recombinant protein antigen (antigen from Bacillus anthracis, causative agent of anthrax) and Th1-skewing resiquimod adjuvant (toll-like receptor 7/8 agonist) either in separate particle sets or co-encapsulated in the same particle. We compare our electrospray formulations in parallel with particles fabricated by solvent evaporation and the FDA-approved anthrax vaccine (BioThrax). Our electrospray formulations administered parenterally lead to increased Th1-skewing antibody production, preserved toxin neutralization, and enhanced protection against an inhaled challenge of the clinically virulent B. anthracis Ames strain. These promising results support electrospray’s potential to be a powerful platform technique for fabricating subunit vaccines and other protein-based drug delivery formulations.

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See more of this Session: Biomaterials for Immunological Applications
See more of this Group/Topical: Materials Engineering and Sciences Division