Next Article in Journal
Development of a Mucoadhesive In Situ Gelling Formulation for the Delivery of Lactobacillus gasseri into Vaginal Cavity
Previous Article in Journal
Preparation, Characterization and Dermal Delivery of Methadone
Article

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

1
Department of Pharmaceutical Technology and Biopharmacy, University of Groningen, Antonius Deusinglaan 1, 9713 AV Groningen, The Netherlands
2
Drug Product Development_Developability, Janssen Research and Development, a Division of Janssen Pharmaceutica NV, Turnhoutseweg 30, 2340 Beerse, Belgium
3
Janssen Vaccines & Prevention B.V., Archimedesweg 4-6, 2333 CN Leiden, The Netherlands
4
Janssen Infectious Diseases and Vaccines, Janssen Research and Development, a Division of Janssen Pharmaceutica NV, Turnhoutseweg 30, 2340 Beerse, Belgium
5
Jalima Pharma bvba, Jozef Van Walleghemstraat 11, 8200 Brugge, Belgium
*
Author to whom correspondence should be addressed.
Both authors contributed equally to this work.
Pharmaceutics 2019, 11(10), 510; https://doi.org/10.3390/pharmaceutics11100510
Received: 5 June 2019 / Revised: 14 September 2019 / Accepted: 30 September 2019 / Published: 3 October 2019
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(dl-lactic-co-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. View Full-Text
Keywords: biphasic pulsatile release; controlled release; freeze-dried powder; fusion protein; poly(dl-lactic-co-glycolic acid); pre-fusion; respiratory syncytial virus; single-injection vaccine biphasic pulsatile release; controlled release; freeze-dried powder; fusion protein; poly(dl-lactic-co-glycolic acid); pre-fusion; respiratory syncytial virus; single-injection vaccine
Show Figures

Figure 1

MDPI and ACS Style

Beugeling, M.; Amssoms, K.; Cox, F.; De Clerck, B.; Van Gulck, E.; Verwoerd, J.A.; Kraus, G.; Roymans, D.; Baert, L.; Frijlink, H.W.; Hinrichs, W.L.J. 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 2019, 11, 510. https://doi.org/10.3390/pharmaceutics11100510

AMA Style

Beugeling M, Amssoms K, Cox F, De Clerck B, Van Gulck E, Verwoerd JA, Kraus G, Roymans D, Baert L, Frijlink HW, Hinrichs WLJ. 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. 2019; 11(10):510. https://doi.org/10.3390/pharmaceutics11100510

Chicago/Turabian Style

Beugeling, Max; Amssoms, Katie; Cox, Freek; De Clerck, Ben; Van Gulck, Ellen; Verwoerd, Jeroen A.; Kraus, Guenter; Roymans, Dirk; Baert, Lieven; Frijlink, Henderik W.; Hinrichs, Wouter L.J. 2019. "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 11, no. 10: 510. https://doi.org/10.3390/pharmaceutics11100510

Find Other Styles
Note that from the first issue of 2016, MDPI journals use article numbers instead of page numbers. See further details here.

Article Access Map by Country/Region

1
Search more from Scilit
 
Search
Back to TopTop