Virus inactivation at moderately low pH varies with virus and buffer properties. Issue 2 (23rd December 2021)

• Record Type: Journal Article
• Authors: Joshi, Pratik U.; Meingast, Christa L.; Xu, Xuankuo; Holstein, Melissa; Feroz, Hasin; Ranjan, Swarnim; Ghose, Sanchayita; Li, Zheng Jian; Heldt, Caryn L.
• Is Part Of: Biotechnology journal. Volume 17:Issue 2(2022)
• Page Start: n/a
• Page End: n/a
• Publication Date: 2021-12-23
• Subjects: arteritis virus -- bioprocessing -- enveloped virus -- herpesvirus -- viral clearance; Biotechnology -- Periodicals; 660.605
• DOI: 10.1002/biot.202100320
• Languages: English
• ISSNs: 1860-6768

Abstract

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. Graphical Abstract and Lay Summary: Low pH virus inactivation is a critical operation in therapeutic protein production. The buffer used to control the pH and the virus used for study effective the amount of virus inactivation measured. In the herpes virus family, pseudorabies virus and herpes simplex virus‐1 cannot be interchanged as model viruses in low pH inactivation studies.