Version 1
: Received: 2 April 2024 / Approved: 3 April 2024 / Online: 3 April 2024 (08:29:17 CEST)
How to cite:
Khan, M.F.H.; Youssef, M.; Nesdoly, S.; Kamen, A.A. Development of a Robust Freeze-drying Process for Long-Term Stability of rVSV-SARS-CoV-2 Vaccine. Preprints2024, 2024040265. https://doi.org/10.20944/preprints202404.0265.v1
Khan, M.F.H.; Youssef, M.; Nesdoly, S.; Kamen, A.A. Development of a Robust Freeze-drying Process for Long-Term Stability of rVSV-SARS-CoV-2 Vaccine. Preprints 2024, 2024040265. https://doi.org/10.20944/preprints202404.0265.v1
Khan, M.F.H.; Youssef, M.; Nesdoly, S.; Kamen, A.A. Development of a Robust Freeze-drying Process for Long-Term Stability of rVSV-SARS-CoV-2 Vaccine. Preprints2024, 2024040265. https://doi.org/10.20944/preprints202404.0265.v1
APA Style
Khan, M.F.H., Youssef, M., Nesdoly, S., & Kamen, A.A. (2024). Development of a Robust Freeze-drying Process for Long-Term Stability of rVSV-SARS-CoV-2 Vaccine. Preprints. https://doi.org/10.20944/preprints202404.0265.v1
Chicago/Turabian Style
Khan, M.F.H., Sean Nesdoly and Amine A. Kamen. 2024 "Development of a Robust Freeze-drying Process for Long-Term Stability of rVSV-SARS-CoV-2 Vaccine" Preprints. https://doi.org/10.20944/preprints202404.0265.v1
Abstract
Abstract: Thermostability of vaccines, particularly enveloped viral vectored vaccines, remains a challenge for their delivery wherever needed. Freeze-drying of viral vectored vaccines is a prom-ising approach but remains challenging due to the water removal process from the outer and in-ner parts of the virus. In the case of enveloped viruses, freeze-drying induces increased stresses on the envelope, which often leads to inactivation of the virus. In this study, we design a method to freeze-dry a recombinant Vesicular Stomatitis Virus (VSV) expressing the SARS-CoV-2 spike glycoprotein. Since the envelope of VSV is composed of 50% lipid and 50% protein, the formula-tion study focused on both the protein and lipid portions of the vector. Formulations were pre-pared primarily using sucrose, trehalose, and sorbitol as cryoprotectants; mannitol as a lyopro-tectant; and histidine as a buffer. Initially, the infectivity of rVSV-SARS-CoV-2 and cake stability were investigated at different final moisture contents. High recovery of the infectious viral titer ( 0.5 to 1 log loss) was found at 3-6% moisture content with no deterioration of the freeze-dried cakes. To further minimize infectious viral titer loss, the composition and concentration of the ex-cipients were studied. An increase from 5 to 10% of both cryoprotectants and lyoprotectant, to-gether with the addition of 0.5% gelatin, resulted in the improved recovery of infectious virus titer and stable cake formation. Moreover, the secondary drying temperature of the freeze-drying pro-cess showed a significant impact on the infectivity of rVSV-SARS-CoV-2. The infectivity of the vector declined drastically when the temperature was raised above 20°C. Throughout a long-term stability study, formulations containing 10% sugar (sucrose/trehalose), 10% mannitol, 0.5% gelatin, and 10 mM of histidine showed satisfactory stability for six months at 2-8°C. The development of this freeze-drying process and the optimized formulation minimizes the need for a costly cold chain distribution system.
Biology and Life Sciences, Biology and Biotechnology
Copyright:
This is an open access article distributed under the Creative Commons Attribution License which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly cited.
