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Efficacy of inactivation of viral contaminants in hyperimmune horse plasma against botulinum toxin by low pH alone and combined with pepsin digestion.

Abstract: Assuring viral safety of horse plasma-derived products is fundamental for ethical and regulatory reasons. We previously demonstrated the ability of pepsin digestion at low pH to inactivate West Nile and Sindbis viruses in horse plasma. The present study further examined the efficiency of pepsin digestion to inactivate four additional viruses: HSV-1 and BVDV (lipid-enveloped), BPV and Reo-3 (nonenveloped). These viruses were spiked into hyperimmunized horse plasma against botulinum toxin and subjected to low pH (3.2) alone or combined with pepsin digestion (1200 units/ml). Peptic digestion inactivated the lipid-enveloped viruses, whereas the nonenveloped viruses were unaffected. Interestingly, HSV-1 was rapidly inactivated by acidic pH alone (≥4.9 ± 0.6 log), whereas a non-robust but meaningful BVDV inactivation (2.9 ± 0.7 log) was achieved by combined low pH and pepsin. The current study demonstrated the ability of low pH alone and in combination with pepsin digestion to inactivate enveloped viral contaminants in anti-toxin horse plasma.
Publication Date: 2017-06-17 PubMed ID: 28633975DOI: 10.1016/j.biologicals.2017.06.003Google Scholar: Lookup
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  • Journal Article

Summary

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The study investigates the effectiveness of using low pH levels, whether alone or combined with pepsin digestion, in deactivating four different types of viruses found in horse plasma. The results showed that this method was able to successfully deactivate enveloped viruses, although non-enveloped viruses were resistant to it.

Objective and Background of the Study

  • The purpose of this research was to ensure the viral safety of products derived from horse plasma for ethical and regulatory purposes. The primary aim was to evaluate the efficacy of pepsin digestion at low pH in the inactivation of HSV-1 and BVDV (lipid-enveloped viruses), and BPV and Reo-3 (nonenveloped viruses) that were added to horse plasma.
  • Prior research by the same team indicated that similar methods were effective at inactivating West Nile and Sindbis viruses in horse plasma. The current study aimed at extending these findings to other viruses.

Methodology and Results

  • HSV-1 and BVDV, and BPV and Reo-3 viruses were introduced into hyperimmunized horse plasma against botulinum toxin. This was then subjected to low pH levels (3.2), with or without accompanying pepsin digestion (at 1200 units/ml).
  • The results showed that pepsin digestion was able to deactivate the lipid-enveloped viruses. However, it was not effective on the nonenveloped viruses.
  • Interestingly, HSV-1 was quickly deactivated just by the low pH, while BVDV showed some resistance, even to the combination of low pH and pepsin. Nevertheless, there were still a meaningful level of BVDV deactivation noted (2.9 ± 0.7 log).

Conclusion

  • The research showed that the use of low pH alone or in combination with pepsin digestion was effective in neutralizing enveloped viral contaminants in anti-toxin horse plasma.
  • However, these methods were not effective on non-enveloped viruses, pointing to the need for further research and alternative techniques to ensure thorough viral inactivation in the varied virus types.

Cite This Article

APA
Torgeman A, Mador N, Dorozko M, Lifshitz A, Eschar N, White MD, Wolf DG, Epstein E. (2017). Efficacy of inactivation of viral contaminants in hyperimmune horse plasma against botulinum toxin by low pH alone and combined with pepsin digestion. Biologicals, 48, 24-27. https://doi.org/10.1016/j.biologicals.2017.06.003

Publication

ISSN: 1095-8320
NlmUniqueID: 9004494
Country: England
Language: English
Volume: 48
Pages: 24-27
PII: S1045-1056(17)30069-6

Researcher Affiliations

Torgeman, Amram
  • Department of Biotechnology, Israel Institute for Biological Research, Ness-Ziona, Israel.
Mador, Nurit
  • Department of Clinical Microbiology and Infectious Diseases, Hadassah University Hospital, 91120 Jerusalem, Israel.
Dorozko, Marina
  • Department of Clinical Microbiology and Infectious Diseases, Hadassah University Hospital, 91120 Jerusalem, Israel.
Lifshitz, Aliza
  • Department of Clinical Microbiology and Infectious Diseases, Hadassah University Hospital, 91120 Jerusalem, Israel.
Eschar, Naomi
  • Hess St, Rehovot, Israel.
White, Moshe D
  • Department of Biotechnology, Israel Institute for Biological Research, Ness-Ziona, Israel.
Wolf, Dana G
  • Department of Clinical Microbiology and Infectious Diseases, Hadassah University Hospital, 91120 Jerusalem, Israel.
Epstein, Eyal
  • Department of Biotechnology, Israel Institute for Biological Research, Ness-Ziona, Israel. Electronic address: eyale@iibr.gov.il.

MeSH Terms

  • Animals
  • Botulinum Antitoxin / chemistry
  • Botulinum Antitoxin / immunology
  • Diarrhea Viruses, Bovine Viral
  • Drug Contamination / prevention & control
  • Herpesvirus 1, Human
  • Horses
  • Hydrogen-Ion Concentration
  • Pepsin A / chemistry
  • Plasma / chemistry
  • Plasma / immunology
  • Plasma / virology
  • Virus Inactivation

Citations

This article has been cited 7 times.
  1. Lee EJ, Han S, Hyun SW, Song GB, Ha SD. Survival of human coronavirus 229E at different temperatures on various food-contact surfaces and food and under simulated digestive conditions.. Food Res Int 2022 Dec;162(Pt A):112014.
    doi: 10.1016/j.foodres.2022.112014pubmed: 36461303google scholar: lookup
  2. Ben David A, Barnea A, Torgeman A, Diamant E, Dor E, Schwartz A, Rosen O, Caspi N, Saraf M, Lerer E, Adar Y, Lupo E, Toister E, Zichel R. Immunologic and Protective Properties of Subunit- vs. Whole Toxoid-Derived Anti-Botulinum Equine Antitoxin.. Vaccines (Basel) 2022 Sep 14;10(9).
    doi: 10.3390/vaccines10091522pubmed: 36146601google scholar: lookup
  3. Rosenfeld R, Alcalay R, Zvi A, Ben-David A, Noy-Porat T, Chitlaru T, Epstein E, Israeli O, Lazar S, Caspi N, Barnea A, Dor E, Chomsky I, Pitel S, Makdasi E, Zichel R, Mazor O. Centaur antibodies: Engineered chimeric equine-human recombinant antibodies.. Front Immunol 2022;13:942317.
    doi: 10.3389/fimmu.2022.942317pubmed: 36059507google scholar: lookup
  4. Torgeman A, Diamant E, Dor E, Schwartz A, Baruchi T, Ben David A, Zichel R. A Rabbit Model for the Evaluation of Drugs for Treating the Chronic Phase of Botulism.. Toxins (Basel) 2021 Sep 24;13(10).
    doi: 10.3390/toxins13100679pubmed: 34678971google scholar: lookup
  5. Schwartz A, Ben David A, Hotoveli M, Dor E, Diamant E, Vivyorka A, Rosen O, Torgeman A, Zichel R. A Novel Running Wheel Mouse Model for Botulism and Its Use for the Evaluation of Postsymptom Antitoxin Efficacy.. Antimicrob Agents Chemother 2021 Jul 16;65(8):e0042121.
    doi: 10.1128/AAC.00421-21pubmed: 33972251google scholar: lookup
  6. Shifman O, Cohen-Gihon I, Beth-Din A, Zvi A, Laskar O, Paran N, Epstein E, Stein D, Dorozko M, Wolf D, Yitzhaki S, Shapira SC, Melamed S, Israeli O. Identification and genetic characterization of a novel Orthobunyavirus species by a straightforward high-throughput sequencing-based approach.. Sci Rep 2019 Mar 4;9(1):3398.
    doi: 10.1038/s41598-019-40036-4pubmed: 30833612google scholar: lookup
  7. Torgeman A, Schwartz A, Diamant E, Baruchi T, Dor E, Ben David A, Pass A, Barnea A, Tal A, Rosner A, Rosen O, Zichel R. Studying the differential efficacy of postsymptom antitoxin treatment in type A versus type B botulism using a rabbit spirometry model.. Dis Model Mech 2018 Sep 27;11(9).
    doi: 10.1242/dmm.035089pubmed: 30115749google scholar: lookup