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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

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Department of Pharmaceutical Technology and Biopharmacy, University of Groningen, Antonius Deusinglaan 1, 9713 AV Groningen, The Netherlands
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Drug Product Development_Developability, Janssen Research and Development, a Division of Janssen Pharmaceutica NV, Turnhoutseweg 30, 2340 Beerse, Belgium
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Janssen Vaccines & Prevention B.V., Archimedesweg 4-6, 2333 CN Leiden, The Netherlands
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Janssen Infectious Diseases and Vaccines, Janssen Research and Development, a Division of Janssen Pharmaceutica NV, Turnhoutseweg 30, 2340 Beerse, Belgium
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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
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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, Katie Amssoms, Freek Cox, Ben De Clerck, Ellen Van Gulck, Jeroen A. Verwoerd, Guenter Kraus, Dirk Roymans, Lieven Baert, Henderik W. Frijlink, and Wouter L.J. Hinrichs. 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

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