TY - JOUR
T1 - Assessment of viral inactivation during pH 3.3 pepsin digestion and caprylic acid treatment of antivenoms
AU - Burnouf, Thierry
AU - Terpstra, Fokke
AU - Habib, George
AU - Seddik, Salwa
PY - 2007/10
Y1 - 2007/10
N2 - 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.
AB - 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.
KW - Acid pH
KW - Antivenom
KW - Caprylate
KW - Horse
KW - Immunoglobulins
KW - Plasma
KW - Safety
KW - Virus
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U2 - 10.1016/j.biologicals.2006.11.003
DO - 10.1016/j.biologicals.2006.11.003
M3 - Article
C2 - 17363271
AN - SCOPUS:35348898600
SN - 1045-1056
VL - 35
SP - 329
EP - 334
JO - Biologicals
JF - Biologicals
IS - 4
ER -