Acetalated Dextran Microparticulate Vaccine Formulated via Coaxial Electrospray Preserves Toxin Neutralization and Enhances Murine Survival Following Inhalational Bacillus Anthracis Exposure.
Subunit formulations are regarded as the safest type of vaccine, but they often contain a protein-based antigen that can result in significant challenges, such as preserving antigenicity during formulation and administration. Many studies have demonstrated that encapsulation of protein antigens in polymeric microparticles (MPs) via emulsion techniques results in total IgG antibody titers comparable to alum formulations, however, the antibodies themselves are non-neutralizing. To address this issue, a coaxial electrohydrodynamic spraying (electrospray) technique is used to formulate a microparticulate-based subunit anthrax vaccine under conditions that minimize recombinant protective antigen (rPA) exposure to harsh solvents and high shear stress. rPA and the adjuvant resiquimod are encapsulated either in separate or the same acetalated dextran MPs. Using a murine model, the electrospray formulations lead to higher IgG2a subtype titers as well as comparable total IgG antibody titers and toxin neutralization relative to the FDA-approved vaccine (BioThrax). BioThrax provides no protection against a lethal inhalational challenge of the highly virulent Ames Bacillus anthracis anthrax strain, whereas 50% of the mice vaccinated with separately encapsulated electrospray MPs survive. Overall, this study demonstrates the potential use of electrospray for encapsulating protein antigens in polymeric MPs.
Department of Chemical and Biomolecular Engineering, College of Engineering, The Ohio State University, Columbus, OH, 43210, USA.|Division of Molecular Pharmaceutics, Eshelman School of Pharmacy, University of North Carolina, Chapel Hill, NC, 27599, USA.
Matthew D
MD
Gallovic
Vaccine and Medical Countermeasures Department, Biological Defense Research Directorate, Naval Medical Research Center, Fort Detrick, MD, 20910, USA.
Kevin L
KL
Schully
Vaccine and Medical Countermeasures Department, Biological Defense Research Directorate, Naval Medical Research Center, Fort Detrick, MD, 20910, USA.
Matthew G
MG
Bell
Vaccine and Medical Countermeasures Department, Biological Defense Research Directorate, Naval Medical Research Center, Fort Detrick, MD, 20910, USA.
Margaret A
MA
Elberson
Vaccine and Medical Countermeasures Department, Biological Defense Research Directorate, Naval Medical Research Center, Fort Detrick, MD, 20910, USA.
John R
JR
Palmer
Vaccine and Medical Countermeasures Department, Biological Defense Research Directorate, Naval Medical Research Center, Fort Detrick, MD, 20910, USA.
Christian A
CA
Darko
Division of Molecular Pharmaceutics, Eshelman School of Pharmacy, University of North Carolina, Chapel Hill, NC, 27599, USA.
Eric M
EM
Bachelder
Department of Chemical and Biomolecular Engineering, College of Engineering, The Ohio State University, Columbus, OH, 43210, USA.|Department of Chemistry and Biochemistry, College of Arts and Sciences, The Ohio State University, Columbus, OH, 43210, USA.
Barbara E
BE
Wyslouzil
Vaccine and Medical Countermeasures Department, Biological Defense Research Directorate, Naval Medical Research Center, Fort Detrick, MD, 20910, USA.
Andrea M
AM
Keane-Myers
Division of Molecular Pharmaceutics, Eshelman School of Pharmacy, University of North Carolina, Chapel Hill, NC, 27599, USA. ainsliek@email.unc.edu.
Kristy M
KM
Ainslie
D000818:Animals; D000881:Anthrax / Q000276:immunology; D022122:Anthrax Vaccines / Q000276:immunology; D057134:Antibodies, Neutralizing / Q000276:immunology*; D000942:Antigens, Bacterial / Q000276:immunology; D001408:Bacillus anthracis / Q000276:immunology*; D001427:Bacterial Toxins / Q000276:immunology*; D002626:Chemistry, Pharmaceutical / Q000379:methods; D003911:Dextrans / Q000737:chemistry* / Q000276:immunology*; D005260:Female; D007074:Immunoglobulin G / Q000276:immunology; D051379:Mice; D008807:Mice, Inbred BALB C; D011108:Polymers / Q000737:chemistry; D014612:Vaccines / Q000737:chemistry* / Q000276:immunology*
D022122:Anthrax Vaccines; D057134:Antibodies, Neutralizing; D000942:Antigens, Bacterial; D001427:Bacterial Toxins; C493276:Biothrax; D003911:Dextrans; D007074:Immunoglobulin G; D011108:Polymers; D014612:Vaccines
Ames challenge; acetalated dextran microparticles; anthrax toxin neutralization; anthrax vaccine; coaxial electrospray