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. 2022 Feb;17(2):e2100320.
doi: 10.1002/biot.202100320. Epub 2021 Dec 23.

Virus inactivation at moderately low pH varies with virus and buffer properties

Pratik U Joshi  1   2 , Christa L Meingast  2   3 , Xuankuo Xu  4 , Melissa Holstein  4 , Hasin Feroz  4 , Swarnim Ranjan  4 , Sanchayita Ghose  4 , Zheng Jian Li  4 , Caryn L Heldt  1   2
Affiliations

Virus inactivation at moderately low pH varies with virus and buffer properties

Pratik U Joshi et al. Biotechnol J. 2022 Feb.

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.

Keywords: arteritis virus; bioprocessing; enveloped virus; herpesvirus; viral clearance.

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