Assessment of viral inactivation during pH 3.3 pepsin digestion and caprylic acid treatment of antivenoms

Thierry Burnouf, Fokke Terpstra, George Habib, Salwa Seddik

Research output: Contribution to journalArticlepeer-review

12 Citations (Scopus)


Antivenoms are manufactured by the fractionation of animal plasma which may possibly be contaminated by infectious agents pathogenic to humans. This study was carried out to determine whether pre-existing antivenom production steps, as carried out by EgyVac in Egypt, may reduce viral risks. Two typical manufacturing steps were studied by performing down-scaled viral inactivation experiments: (a) a pH 3.3 pepsin digestion of diluted plasma at 30 °C for 1 h, and (b) a caprylic acid treatment of a purified F(ab′)2 fragment fraction at 18 °C for 1 h. Three lipid-enveloped (LE) viruses [bovine viral diarrhoea virus (BVDV), pseudorabies virus (PRV), and vesicular stomatitis virus (VSV)] and one non-lipid-enveloped (NLE) virus [encephalomyocarditis virus (EMC)] were used as models. Kinetics of inactivation was determined by taking samples at 3 time-points during the treatments. The pH 3.3 pepsin digestion resulted in complete clearance of PRV (>7.0 log10) and in almost complete reduction of VSV (>4.5 but ≤6.4 log10), and in a limited inactivation of BVDV (1.7 log10). EMC inactivation was ≥2.5 but ≤5.7 log10. The caprylic acid treatment resulted in complete inactivation of the 3 LE viruses tested: BVDV (>6.6 log10), PRV (>6.6 log10), and VSV (>7.0 log10). For EMC no significant reduction was obtained (0.7 log10). Cumulative reduction was >13.6, >11.5, >8.3 and ≥2.5 for PRV, VSV, BVDV and EMC, respectively. Therefore the current manufacturing processes of at least some animal antisera already include production steps that can ensure robust viral inactivation of LE viruses and moderate inactivation of a NLE virus.

Original languageEnglish
Pages (from-to)329-334
Number of pages6
Issue number4
Publication statusPublished - Oct 2007
Externally publishedYes


  • Acid pH
  • Antivenom
  • Caprylate
  • Horse
  • Immunoglobulins
  • Plasma
  • Safety
  • Virus

ASJC Scopus subject areas

  • Immunology
  • Microbiology
  • Infectious Diseases


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