[Inactivation of BVDV (experimental model for hepatitis C) using low pH and heat treatment in intravenous human immunoglobulins].
OBJECTIVE
To measure the capability of heat (60 degrees C for 10 hr) and low pH to inactivate BVDV (a model of HCV) in human intravenous immunoglobulins.


METHODS
The study was carried out on three batches of immunoglobulins produced by the Cohn method and contaminated with a known amount of BVDV. These mixtures, with and without 33% sorbitol, were submitted to heat treatment at 60 degrees C for 10 hours. The same immunoglobulin batches were manufactured at pH 4.25 and 4.5 and stored at 4 degrees C and 4 degrees C and 21 degrees C for 28 days. Samples of the two experiments were taken at the beginning and the end. The viral infectiousness was calculated by the standard microtiration method in 96-well plates, using the CPE, and the reduction factor was measured for each experiment.


RESULTS
Complete viral inactivation was achieved with the heat treatment after 4 hours, and the 33% sorbitol decreased the formation of aggregates. Treatment by pH 4.5, at 21 degrees C for 28 days, decreased the viral load by approximately 2 log; no viral inactivation was achieved in samples stored at 4 degrees C.


CONCLUSIONS
Heat is an effective method for inactivating HCV in final batches of human intravenous immunoglobulins when 33% sorbitol is added. The use of low pH at 21 degrees C as a method of viral inactivation must be evaluated case by case, since, according to the present results, it only achieved a 2 log inactivation.
Ruibal Brunet
I J
IJ
Laboratorio de Investigaciones del SIDA, Ciudad de La Habana, Cuba.
Noa Romero
E
E
Rivero Mas
A T
AT
Martín García
R Z
RZ
D000818:Animals; D002417:Cattle; D002460:Cell Line; D002852:Chromatography, Ion Exchange; D003080:Cold Temperature; D001908:Diarrhea Viruses, Bovine Viral / Q000187:drug effects / Q000302:isolation & purification / Q000502:physiology; D016174:Hepacivirus; D006358:Hot Temperature; D006801:Humans; D006863:Hydrogen-Ion Concentration; D016756:Immunoglobulins, Intravenous / Q000302:isolation & purification*; D011489:Protein Denaturation; D012449:Safety; D013012:Sorbitol / Q000494:pharmacology; D013242:Sterilization / Q000379:methods*; D019562:Viral Load; D014764:Viral Proteins / Q000737:chemistry / Q000187:drug effects; D014776:Virus Cultivation; D014779:Virus Replication / Q000187:drug effects
D016756:Immunoglobulins, Intravenous; D014764:Viral Proteins; D013012:Sorbitol