Crystallization of a nonreplicating rotavirus vaccine candidate
Name
bit.27699.pdf
Description
Published version
Size
1.41 MB
Format
Unknown
Checksum (MD5)
e35d8aa9f81e62c78c060967bd57444a
Author(s)
Hong, Moo Sun
Kaur, Kawaljit
Sawant, Nishant
Joshi, Sangeeta B.
Volkin, David B.
Braatz, Richard D.
Date Issued
February 2021
Journal
Biotechnology and Bioengineering
Publisher
Wiley
Version
Final published version
Abstract
Nonreplicating rotavirus vaccine (NRRV) candidates are being developed with the aim of serving the needs of developing countries. A significant proportion of the cost of manufacturing such vaccines is the purification in multiple chromatography steps. Crystallization has the potential to reduce purification costs and provide new product storage modality, improved operational flexibility, and reduced facility footprints. This communication describes a systematic approach for the design of the crystallization of an NRRV candidate, VP8 subunit proteins fused to the P2 epitope of tetanus toxin, using first-principles models and preliminary experimental data. The first-principles models are applied to literature data to obtain feasible crystallization conditions and lower bounds for nucleation and growth rates. Crystallization is then performed in a hanging-drop vapor diffusion system, resulting in the nucleation and growth of NRRV crystals. The crystals obtained in a scaled-up evaporative crystallization contain proteins truncated in the P2 region, but have no significant differences with the original samples in terms of antibody binding and overall conformational stability. These results demonstrate the promise of evaporative crystallization of the NRRV.
MIT Department
Massachusetts Institute of Technology. Department of Chemical Engineering
Terms of Use
Creative Commons Attribution 4.0 International license
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DOI of Published Version
https://doi.org/10.1002/bit.27699
