Development of a Stable Respiratory Syncytial Virus Pre-Fusion Protein Powder Suitable for a Core-Shell Implant with a Delayed Release in Mice: A Proof of Concept Study
Currently, there is an increasing interest to apply pre-fusion (pre-F) protein of respiratory syncytial virus (RSV) as antigen for the development of a subunit vaccine. A pre-F-containing powder would increase the flexibility regarding the route of administration. For instance, a pre-F-containing po...
| Main Authors: | , , , , , , , , , , |
|---|---|
| Format: | Article |
| Language: | English |
| Published: |
MDPI AG
2019-10-01
|
| Series: | Pharmaceutics |
| Subjects: | |
| Online Access: | https://www.mdpi.com/1999-4923/11/10/510 |
| _version_ | 1798035364659593216 |
|---|---|
| author | Max Beugeling Katie Amssoms Freek Cox Ben De Clerck Ellen Van Gulck Jeroen A. Verwoerd Guenter Kraus Dirk Roymans Lieven Baert Henderik W. Frijlink Wouter L. J. Hinrichs |
| author_facet | Max Beugeling Katie Amssoms Freek Cox Ben De Clerck Ellen Van Gulck Jeroen A. Verwoerd Guenter Kraus Dirk Roymans Lieven Baert Henderik W. Frijlink Wouter L. J. Hinrichs |
| author_sort | Max Beugeling |
| collection | DOAJ |
| description | Currently, there is an increasing interest to apply pre-fusion (pre-F) protein of respiratory syncytial virus (RSV) as antigen for the development of a subunit vaccine. A pre-F-containing powder would increase the flexibility regarding the route of administration. For instance, a pre-F-containing powder could be incorporated into a single-injection system releasing a primer, and after a lag time, a booster. The most challenging aspect, obtaining the booster after a lag time, may be achieved by incorporating the powder into a core encapsulated by a nonporous poly(<span style="font-variant: small-caps;">dl</span>-lactic-<i>co</i>-glycolic acid) (PLGA) shell. We intended to develop a stable freeze-dried pre-F-containing powder. Furthermore, we investigated whether incorporation of this powder into the core-shell implant was feasible and whether this system would induce a delayed RSV virus-neutralizing antibody (VNA) response in mice. The developed pre-F-containing powder, consisting of pre-F in a matrix of inulin, HEPES, sodium chloride, and Tween 80, was stable during freeze-drying and storage for at least 28 days at 60 °C. Incorporation of this powder into the core-shell implant was feasible and the core-shell production process did not affect the stability of pre-F. An in vitro release study showed that pre-F was incompletely released from the core-shell implant after a lag time of 4 weeks. The incomplete release may be the result of pre-F instability within the core-shell implant during the lag time and requires further research. Mice subcutaneously immunized with a pre-F-containing core-shell implant showed a delayed RSV VNA response that corresponded with pre-F release from the core-shell implant after a lag time of approximately 4 weeks. Moreover, pre-F-containing core-shell implants were able to boost RSV VNA titers of primed mice after a lag time of 4 weeks. These findings could contribute to the development of a single-injection pre-F-based vaccine containing a primer and a booster. |
| first_indexed | 2024-04-11T20:57:09Z |
| format | Article |
| id | doaj.art-1fab9f6aa5144ad296de6c6ca8e08c85 |
| institution | Directory Open Access Journal |
| issn | 1999-4923 |
| language | English |
| last_indexed | 2024-04-11T20:57:09Z |
| publishDate | 2019-10-01 |
| publisher | MDPI AG |
| record_format | Article |
| series | Pharmaceutics |
| spelling | doaj.art-1fab9f6aa5144ad296de6c6ca8e08c852022-12-22T04:03:38ZengMDPI AGPharmaceutics1999-49232019-10-01111051010.3390/pharmaceutics11100510pharmaceutics11100510Development of a Stable Respiratory Syncytial Virus Pre-Fusion Protein Powder Suitable for a Core-Shell Implant with a Delayed Release in Mice: A Proof of Concept StudyMax Beugeling0Katie Amssoms1Freek Cox2Ben De Clerck3Ellen Van Gulck4Jeroen A. Verwoerd5Guenter Kraus6Dirk Roymans7Lieven Baert8Henderik W. Frijlink9Wouter L. J. Hinrichs10Department of Pharmaceutical Technology and Biopharmacy, University of Groningen, Antonius Deusinglaan 1, 9713 AV Groningen, The NetherlandsDrug Product Development_Developability, Janssen Research and Development, a Division of Janssen Pharmaceutica NV, Turnhoutseweg 30, 2340 Beerse, BelgiumJanssen Vaccines & Prevention B.V., Archimedesweg 4-6, 2333 CN Leiden, The NetherlandsJanssen Infectious Diseases and Vaccines, Janssen Research and Development, a Division of Janssen Pharmaceutica NV, Turnhoutseweg 30, 2340 Beerse, BelgiumJanssen Infectious Diseases and Vaccines, Janssen Research and Development, a Division of Janssen Pharmaceutica NV, Turnhoutseweg 30, 2340 Beerse, BelgiumDepartment of Pharmaceutical Technology and Biopharmacy, University of Groningen, Antonius Deusinglaan 1, 9713 AV Groningen, The NetherlandsJanssen Infectious Diseases and Vaccines, Janssen Research and Development, a Division of Janssen Pharmaceutica NV, Turnhoutseweg 30, 2340 Beerse, BelgiumJanssen Infectious Diseases and Vaccines, Janssen Research and Development, a Division of Janssen Pharmaceutica NV, Turnhoutseweg 30, 2340 Beerse, BelgiumJalima Pharma bvba, Jozef Van Walleghemstraat 11, 8200 Brugge, BelgiumDepartment of Pharmaceutical Technology and Biopharmacy, University of Groningen, Antonius Deusinglaan 1, 9713 AV Groningen, The NetherlandsDepartment of Pharmaceutical Technology and Biopharmacy, University of Groningen, Antonius Deusinglaan 1, 9713 AV Groningen, The NetherlandsCurrently, there is an increasing interest to apply pre-fusion (pre-F) protein of respiratory syncytial virus (RSV) as antigen for the development of a subunit vaccine. A pre-F-containing powder would increase the flexibility regarding the route of administration. For instance, a pre-F-containing powder could be incorporated into a single-injection system releasing a primer, and after a lag time, a booster. The most challenging aspect, obtaining the booster after a lag time, may be achieved by incorporating the powder into a core encapsulated by a nonporous poly(<span style="font-variant: small-caps;">dl</span>-lactic-<i>co</i>-glycolic acid) (PLGA) shell. We intended to develop a stable freeze-dried pre-F-containing powder. Furthermore, we investigated whether incorporation of this powder into the core-shell implant was feasible and whether this system would induce a delayed RSV virus-neutralizing antibody (VNA) response in mice. The developed pre-F-containing powder, consisting of pre-F in a matrix of inulin, HEPES, sodium chloride, and Tween 80, was stable during freeze-drying and storage for at least 28 days at 60 °C. Incorporation of this powder into the core-shell implant was feasible and the core-shell production process did not affect the stability of pre-F. An in vitro release study showed that pre-F was incompletely released from the core-shell implant after a lag time of 4 weeks. The incomplete release may be the result of pre-F instability within the core-shell implant during the lag time and requires further research. Mice subcutaneously immunized with a pre-F-containing core-shell implant showed a delayed RSV VNA response that corresponded with pre-F release from the core-shell implant after a lag time of approximately 4 weeks. Moreover, pre-F-containing core-shell implants were able to boost RSV VNA titers of primed mice after a lag time of 4 weeks. These findings could contribute to the development of a single-injection pre-F-based vaccine containing a primer and a booster.https://www.mdpi.com/1999-4923/11/10/510biphasic pulsatile releasecontrolled releasefreeze-dried powderfusion proteinpoly(<span style="font-variant: small-caps">dl</span>-lactic-<i>co</i>-glycolic acid)pre-fusionrespiratory syncytial virussingle-injection vaccine |
| spellingShingle | Max Beugeling Katie Amssoms Freek Cox Ben De Clerck Ellen Van Gulck Jeroen A. Verwoerd Guenter Kraus Dirk Roymans Lieven Baert Henderik W. Frijlink Wouter L. J. Hinrichs Development of a Stable Respiratory Syncytial Virus Pre-Fusion Protein Powder Suitable for a Core-Shell Implant with a Delayed Release in Mice: A Proof of Concept Study Pharmaceutics biphasic pulsatile release controlled release freeze-dried powder fusion protein poly(<span style="font-variant: small-caps">dl</span>-lactic-<i>co</i>-glycolic acid) pre-fusion respiratory syncytial virus single-injection vaccine |
| title | Development of a Stable Respiratory Syncytial Virus Pre-Fusion Protein Powder Suitable for a Core-Shell Implant with a Delayed Release in Mice: A Proof of Concept Study |
| title_full | Development of a Stable Respiratory Syncytial Virus Pre-Fusion Protein Powder Suitable for a Core-Shell Implant with a Delayed Release in Mice: A Proof of Concept Study |
| title_fullStr | Development of a Stable Respiratory Syncytial Virus Pre-Fusion Protein Powder Suitable for a Core-Shell Implant with a Delayed Release in Mice: A Proof of Concept Study |
| title_full_unstemmed | Development of a Stable Respiratory Syncytial Virus Pre-Fusion Protein Powder Suitable for a Core-Shell Implant with a Delayed Release in Mice: A Proof of Concept Study |
| title_short | Development of a Stable Respiratory Syncytial Virus Pre-Fusion Protein Powder Suitable for a Core-Shell Implant with a Delayed Release in Mice: A Proof of Concept Study |
| title_sort | development of a stable respiratory syncytial virus pre fusion protein powder suitable for a core shell implant with a delayed release in mice a proof of concept study |
| topic | biphasic pulsatile release controlled release freeze-dried powder fusion protein poly(<span style="font-variant: small-caps">dl</span>-lactic-<i>co</i>-glycolic acid) pre-fusion respiratory syncytial virus single-injection vaccine |
| url | https://www.mdpi.com/1999-4923/11/10/510 |
| work_keys_str_mv | AT maxbeugeling developmentofastablerespiratorysyncytialvirusprefusionproteinpowdersuitableforacoreshellimplantwithadelayedreleaseinmiceaproofofconceptstudy AT katieamssoms developmentofastablerespiratorysyncytialvirusprefusionproteinpowdersuitableforacoreshellimplantwithadelayedreleaseinmiceaproofofconceptstudy AT freekcox developmentofastablerespiratorysyncytialvirusprefusionproteinpowdersuitableforacoreshellimplantwithadelayedreleaseinmiceaproofofconceptstudy AT bendeclerck developmentofastablerespiratorysyncytialvirusprefusionproteinpowdersuitableforacoreshellimplantwithadelayedreleaseinmiceaproofofconceptstudy AT ellenvangulck developmentofastablerespiratorysyncytialvirusprefusionproteinpowdersuitableforacoreshellimplantwithadelayedreleaseinmiceaproofofconceptstudy AT jeroenaverwoerd developmentofastablerespiratorysyncytialvirusprefusionproteinpowdersuitableforacoreshellimplantwithadelayedreleaseinmiceaproofofconceptstudy AT guenterkraus developmentofastablerespiratorysyncytialvirusprefusionproteinpowdersuitableforacoreshellimplantwithadelayedreleaseinmiceaproofofconceptstudy AT dirkroymans developmentofastablerespiratorysyncytialvirusprefusionproteinpowdersuitableforacoreshellimplantwithadelayedreleaseinmiceaproofofconceptstudy AT lievenbaert developmentofastablerespiratorysyncytialvirusprefusionproteinpowdersuitableforacoreshellimplantwithadelayedreleaseinmiceaproofofconceptstudy AT henderikwfrijlink developmentofastablerespiratorysyncytialvirusprefusionproteinpowdersuitableforacoreshellimplantwithadelayedreleaseinmiceaproofofconceptstudy AT wouterljhinrichs developmentofastablerespiratorysyncytialvirusprefusionproteinpowdersuitableforacoreshellimplantwithadelayedreleaseinmiceaproofofconceptstudy |