Antigen delivery format variation and formulation stability through use of a hybrid vector
A hybrid biological-biomaterial antigen delivery vector comprised of a polymeric shell encapsulating an Escherichia coli core was previously developed for in situ antigen production and subsequent delivery. Due to the engineering capacity of the bacterial core, the hybrid vector provides unique oppo...
| Main Authors: | , , , , , , , , , |
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| Format: | Article |
| Language: | English |
| Published: |
Elsevier
2019-04-01
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| Series: | Vaccine: X |
| Online Access: | http://www.sciencedirect.com/science/article/pii/S2590136219300130 |
| _version_ | 1818486556894167040 |
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| author | Marie Beitelshees Andrew Hill Yi Li Mingfu Chen Mahmoud Kamal Ahmadi Randall J. Smith, Jr Stelios T. Andreadis Pooya Rostami Charles H. Jones Blaine A. Pfeifer |
| author_facet | Marie Beitelshees Andrew Hill Yi Li Mingfu Chen Mahmoud Kamal Ahmadi Randall J. Smith, Jr Stelios T. Andreadis Pooya Rostami Charles H. Jones Blaine A. Pfeifer |
| author_sort | Marie Beitelshees |
| collection | DOAJ |
| description | A hybrid biological-biomaterial antigen delivery vector comprised of a polymeric shell encapsulating an Escherichia coli core was previously developed for in situ antigen production and subsequent delivery. Due to the engineering capacity of the bacterial core, the hybrid vector provides unique opportunities for immunogenicity optimization through varying cellular localization (cytoplasm, periplasm, cellular surface) and type (protein or DNA) of antigen. In this work, three protein-based hybrid vector formats were compared in which the pneumococcal surface protein A (PspA) was localized to the cytoplasm, surface, and periplasmic space of the bacterial core for vaccination against pneumococcal disease. Furthermore, we tested the hybrid vector’s capacity as a DNA vaccine against Streptococcus pneumoniae by introducing a plasmid into the bacterial core to facilitate PspA expression in antigen presenting cells (APCs). Through testing these various formulations, we determined that cytoplasmic accumulation of PspA elicited the strongest immune response (antibody production and protection against bacterial challenge) and enabled complete protection at substantially lower doses when compared to vaccination with PspA + adjuvant. We also improved the storage stability of the hybrid vector to retain complete activity after 1 month at 4 °C using an approach in which hybrid vectors suspended in a microbial freeze drying buffer were desiccated. These results demonstrate the flexibility and robustness of the hybrid vector formulation, which has the potential to be a potent vaccine against S. pneumoniae. Keywords: Vaccine delivery, DNA vaccine, Pneumococcal disease, Streptococcus pneumoniae, Pneumococcal surface protein A (PspA) |
| first_indexed | 2024-12-10T16:24:33Z |
| format | Article |
| id | doaj.art-1a8e159e5dbe47ebb2a0dc34caea7338 |
| institution | Directory Open Access Journal |
| issn | 2590-1362 |
| language | English |
| last_indexed | 2024-12-10T16:24:33Z |
| publishDate | 2019-04-01 |
| publisher | Elsevier |
| record_format | Article |
| series | Vaccine: X |
| spelling | doaj.art-1a8e159e5dbe47ebb2a0dc34caea73382022-12-22T01:41:42ZengElsevierVaccine: X2590-13622019-04-011Antigen delivery format variation and formulation stability through use of a hybrid vectorMarie Beitelshees0Andrew Hill1Yi Li2Mingfu Chen3Mahmoud Kamal Ahmadi4Randall J. Smith, Jr5Stelios T. Andreadis6Pooya Rostami7Charles H. Jones8Blaine A. Pfeifer9Department of Chemical and Biological Engineering, University at Buffalo, The State University of New York, Buffalo, NY 14260-4200, USADepartment 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, USADepartment of Chemical and Biological Engineering, University at Buffalo, The State University of New York, Buffalo, NY 14260-4200, USADepartment of Chemical and Biological Engineering, University at Buffalo, The State University of New York, Buffalo, NY 14260-4200, USADepartment of Chemical and Biological Engineering, University at Buffalo, The State University of New York, Buffalo, NY 14260-4200, USADepartment of Biomedical Engineering, University at Buffalo, The State University of New York, Buffalo, NY 14260-4200, USADepartment 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, USAAbcombi Biosciences Inc., Buffalo, NY 14260-4200, USAAbcombi Biosciences Inc., Buffalo, NY 14260-4200, USADepartment 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; Corresponding author at: Department of Chemical and Biological Engineering, University at Buffalo, The State University of New York, Buffalo, NY 14260-4200, USA.A hybrid biological-biomaterial antigen delivery vector comprised of a polymeric shell encapsulating an Escherichia coli core was previously developed for in situ antigen production and subsequent delivery. Due to the engineering capacity of the bacterial core, the hybrid vector provides unique opportunities for immunogenicity optimization through varying cellular localization (cytoplasm, periplasm, cellular surface) and type (protein or DNA) of antigen. In this work, three protein-based hybrid vector formats were compared in which the pneumococcal surface protein A (PspA) was localized to the cytoplasm, surface, and periplasmic space of the bacterial core for vaccination against pneumococcal disease. Furthermore, we tested the hybrid vector’s capacity as a DNA vaccine against Streptococcus pneumoniae by introducing a plasmid into the bacterial core to facilitate PspA expression in antigen presenting cells (APCs). Through testing these various formulations, we determined that cytoplasmic accumulation of PspA elicited the strongest immune response (antibody production and protection against bacterial challenge) and enabled complete protection at substantially lower doses when compared to vaccination with PspA + adjuvant. We also improved the storage stability of the hybrid vector to retain complete activity after 1 month at 4 °C using an approach in which hybrid vectors suspended in a microbial freeze drying buffer were desiccated. These results demonstrate the flexibility and robustness of the hybrid vector formulation, which has the potential to be a potent vaccine against S. pneumoniae. Keywords: Vaccine delivery, DNA vaccine, Pneumococcal disease, Streptococcus pneumoniae, Pneumococcal surface protein A (PspA)http://www.sciencedirect.com/science/article/pii/S2590136219300130 |
| spellingShingle | Marie Beitelshees Andrew Hill Yi Li Mingfu Chen Mahmoud Kamal Ahmadi Randall J. Smith, Jr Stelios T. Andreadis Pooya Rostami Charles H. Jones Blaine A. Pfeifer Antigen delivery format variation and formulation stability through use of a hybrid vector Vaccine: X |
| title | Antigen delivery format variation and formulation stability through use of a hybrid vector |
| title_full | Antigen delivery format variation and formulation stability through use of a hybrid vector |
| title_fullStr | Antigen delivery format variation and formulation stability through use of a hybrid vector |
| title_full_unstemmed | Antigen delivery format variation and formulation stability through use of a hybrid vector |
| title_short | Antigen delivery format variation and formulation stability through use of a hybrid vector |
| title_sort | antigen delivery format variation and formulation stability through use of a hybrid vector |
| url | http://www.sciencedirect.com/science/article/pii/S2590136219300130 |
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