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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

Beugeling, M., Amssoms, K., Cox, F., De Clerck, B., Van Gulck, E., Verwoerd, J., Kraus, G., Roymans, D., Baert, L., Frijlink, H. W. & Hinrichs, W., Oct-2019, In : Pharmaceutics. 11, 10, 18 p., 510.

Research output: Contribution to journalArticleAcademicpeer-review

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 degrees 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.

Original languageEnglish
Article number510
Number of pages18
JournalPharmaceutics
Volume11
Issue number10
Publication statusPublished - Oct-2019

    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, POLY(LACTIDE-CO-GLYCOLIDE) IMPLANTS, VACCINE POWDER, STABILIZATION, MECHANISMS, CHALLENGES, COMPLETENESS, FORMULATIONS, DEGRADATION, INSTABILITY, TECHNOLOGY

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