title: In situ pneumococcal vaccine production and delivery through a hybrid biological-biomaterial vector.
abstract: The type and potency of an immune response provoked during vaccination will determine ultimate success in disease prevention. The basis for this response will be the design and implementation of antigen presentation to the immune system. Whereas direct antigen administration will elicit some form of immunological response, a more sophisticated approach would couple the antigen of interest to a vector capable of broad delivery formats and designed for heightened response. New antigens associated with pneumococcal disease virulence were used to test the delivery and adjuvant capabilities of a hybrid biological-biomaterial vector consisting of a bacterial core electrostatically coated with a cationic polymer. The hybrid design provides (i) passive and active targeting of antigen-presenting cells, (ii) natural and multicomponent adjuvant properties, (iii) dual intracellular delivery mechanisms, and (iv) a simple formulation mechanism. In addition, the hybrid format enables device-specific, or in situ, antigen production and consolidation via localization within the bacterial component of the vector. This capability eliminates the need for dedicated antigen production and purification before vaccination efforts while leveraging the aforementioned features of the overall delivery device. We present the first disease-specific utilization of the vector toward pneumococcal disease highlighted by improved immune responses and protective capabilities when tested against traditional vaccine formulations and a range of clinically relevant Streptococcus pneumoniae strains. More broadly, the results point to similar levels of success with other diseases that would benefit from the production, delivery, and efficacy capabilities offered by the hybrid vector.
authors.affiliation: Department of Chemical and Biological Engineering, University at Buffalo, The State University of New York, Buffalo, NY 14260-4200, USA.
authors.forename: Yi
authors.initials: Y
authors.lastname: Li
authors.affiliation: Department of Chemical and Biological Engineering, University at Buffalo, The State University of New York, Buffalo, NY 14260-4200, USA.
authors.forename: Marie
authors.initials: M
authors.lastname: Beitelshees
authors.affiliation: Department of Chemical and Biological Engineering, University at Buffalo, The State University of New York, Buffalo, NY 14260-4200, USA.
authors.forename: Lei
authors.initials: L
authors.lastname: Fang
authors.affiliation: Abcombi Biosciences Inc., Buffalo, NY 14260-4200, USA.
authors.forename: Andrew
authors.initials: A
authors.lastname: Hill
authors.affiliation: Department of Chemical and Biological Engineering, University at Buffalo, The State University of New York, Buffalo, NY 14260-4200, USA.
authors.forename: Mahmoud Kamal
authors.initials: MK
authors.lastname: Ahmadi
authors.affiliation: Department of Chemical and Biological Engineering, University at Buffalo, The State University of New York, Buffalo, NY 14260-4200, USA.
authors.forename: Mingfu
authors.identifier: 0000-0002-0169-613X
authors.initials: M
authors.lastname: Chen
authors.affiliation: Department of Anesthesiology, University at Buffalo, The State University of New York, Buffalo, NY 14260-4200, USA.
authors.forename: Bruce A
authors.identifier: 0000-0001-8223-1870
authors.initials: BA
authors.lastname: Davidson
authors.affiliation: Department of Anesthesiology, University at Buffalo, The State University of New York, Buffalo, NY 14260-4200, USA.; Department of Microbiology and Immunology, University at Buffalo, The State University of New York, Buffalo, NY 14260-4200, USA.
authors.forename: Paul
authors.identifier: 0000-0002-9201-3305
authors.initials: P
authors.lastname: Knight
authors.affiliation: Department of Biomedical Engineering, University at Buffalo, The State University of New York, Buffalo, NY 14260-4200, USA.
authors.forename: Randall J
authors.initials: RJ
authors.lastname: Smith
authors.affiliation: Department of Chemical and Biological Engineering, University at Buffalo, The State University of New York, Buffalo, NY 14260-4200, USA.; Department of Biomedical Engineering, University at Buffalo, The State University of New York, Buffalo, NY 14260-4200, USA.; Center of Excellence in Bioinformatics and Life Sciences, Buffalo, NY 14203, USA.
authors.forename: Stelios T
authors.initials: ST
authors.lastname: Andreadis
authors.affiliation: Department of Microbiology and Immunology, University at Buffalo, The State University of New York, Buffalo, NY 14260-4200, USA.; Division of Experimental Infection Medicine, Department of Laboratory Medicine, Lund University, Malmö SE-20502, Sweden.
authors.forename: Anders P
authors.identifier: 0000-0002-2834-6009
authors.initials: AP
authors.lastname: Hakansson
authors.affiliation: Department of Chemical and Biological Engineering, University at Buffalo, The State University of New York, Buffalo, NY 14260-4200, USA.; Abcombi Biosciences Inc., Buffalo, NY 14260-4200, USA.
authors.forename: Charles H
authors.initials: CH
authors.lastname: Jones
authors.affiliation: Department of Chemical and Biological Engineering, University at Buffalo, The State University of New York, Buffalo, NY 14260-4200, USA.; Abcombi Biosciences Inc., Buffalo, NY 14260-4200, USA.
authors.forename: Blaine A
authors.initials: BA
authors.lastname: Pfeifer
mesh_terms: D000276:Adjuvants, Immunologic; D000818:Animals; D000942:Antigens, Bacterial / Q000235:genetics / Q000276:immunology / Q000378:metabolism; D001426:Bacterial Proteins / Q000235:genetics / Q000276:immunology / Q000378:metabolism; D001672:Biocompatible Materials / Q000737:chemistry*; D004195:Disease Models, Animal; D005260:Female; D051379:Mice; D009305:Nasopharynx / Q000382:microbiology; D011008:Pneumococcal Infections / Q000276:immunology / Q000517:prevention & control / Q000662:veterinary; D022242:Pneumococcal Vaccines / Q000737:chemistry / Q000276:immunology*; D011108:Polymers / Q000737:chemistry; D013296:Streptococcus pneumoniae / Q000378:metabolism / Q000472:pathogenicity; D014614:Vaccines, Synthetic / Q000276:immunology
chemical_list: D000276:Adjuvants, Immunologic; D000942:Antigens, Bacterial; D001426:Bacterial Proteins; D001672:Biocompatible Materials; D022242:Pneumococcal Vaccines; D011108:Polymers; D014614:Vaccines, Synthetic; C507253:poly(beta-amino ester)
keywords: Antigen delivery; biological vector; biomaterials; pneumococcal disease; vaccine