Virus inactivation at moderately low pH varies with virus and buffer properties
Document Type
Article
Publication Date
1-1-2021
Abstract
Background: Virus inactivation is a critical operation in therapeutic protein manufacturing. Low pH buffers are a widely used strategy to ensure robust enveloped virus clearance. However, the choice of model virus can give varying results in viral clearance studies. Pseudorabies virus (SuHV) or herpes simplex virus-1 (HSV-1) are frequently chosen as model viruses to demonstrate the inactivation for the herpes family. Results: In this study, SuHV, HSV-1, and equine arteritis virus (EAV) were used to compare the inactivation susceptibility at pH 4.0 and 4°C. SuHV and HSV-1 are from the same family, and EAV was chosen as a small, enveloped virus. Glycine, acetate, and citrate buffers at pH 4.0 and varying buffer strengths were studied. The inactivation susceptibility was found to be in the order of SuHV > HSV > EAV. The buffer effectiveness was found to be in the order of citrate > acetate > glycine. The smaller virus, EAV, remained stable and infectious in all the buffer types and compositions studied. Conclusion: The variation in inactivation susceptibility of herpes viruses indicated that SuHV and HSV cannot be interchangeably used as a virus model for inactivation studies. Smaller viruses might remain adventitiously infective at moderately low pH.
Publication Title
Biotechnology Journal
Recommended Citation
Joshi, P.,
Meingast, C.,
Xu, X.,
Holstein, M.,
Feroz, H.,
Ranjan, S.,
Ghose, S.,
Li, Z.,
&
Heldt, C.
(2021).
Virus inactivation at moderately low pH varies with virus and buffer properties.
Biotechnology Journal.
http://doi.org/10.1002/biot.202100320
Retrieved from: https://digitalcommons.mtu.edu/michigantech-p/15609