Validation of betapropiolactone (BPL) as an inactivant for infectious bovine rhinotracheitis (IBR) virus.

Infectious bovine rhinotracheitis (IBR) virus causes vulvovaginitis, abortion and respiratory disease in cows and heifers. Betapropiolactone (BPL) is a disinfectant, effective against bacteria, fungi and viruses. It is also used to prepare inactivated vaccines because it destroys the nucleic acid core of viruses but does not damage the capsid. For the validation of BPL when used as an inactivant, it is more important to assure the quality of inactivating agent and the validity of the inactivation process. In the present study, the inactivation kinetics of IBR virus was determined with different concentration of BPL (1:250, 1:500, 1:1000, 1:1500, 1:2000 and 1:2500) at 4 and 37 degrees C. The result indicated that the BPL at 4 degrees C was able to inactivate the IBR virus within 4, 5 and 12h with the concentration of 1:250, 1:500 and 1:1000, respectively. BPL at 37 degrees C was able to inactivate virus within 30 min with the concentration of 1:250. BPL with the concentration of 1:500 and 1:1000 were able to inactivate the virus within 120 min at 37 degrees C. Based on the kinetic study seven formulations were prepared and a sero conversion study of IBR inactivated vaccine was carried out. Serological response in animals to different formulations did not differ significantly (P>0.05).

Beta-propiolactone for the inactivation of non-A/non-B type 1 hepatitis virus capable of inducing cytoplasmic tubular ultrastructures in chimpanzees.

Non-A/Non-B type 1 hepatitis virus may be recognized because it induces characteristic tubular ultrastructures in the hepatocyte cytoplasm of chimpanzees. 3 chimps received 0.1 ml of a chimp serum containing more than 100 chimp infecting units of non-A/non-B type 1 hepatitis virus after it had been treated with beta-propiolactone with or without combined ultraviolet irradiation. All of the chimps escaped infection throughout the observation period of 23 weeks. The treatment of the serum with beta-propiolactone at the mildest condition employed (0.05%, 4 degrees C, 20 min) was still effective in inactivating the virus. The susceptibility of the chimps was ascertained by the subsequent challenge with 0.1 ml of the untreated serum which invariably induced non-A/non-B type 1 hepatitis in them. On the basis of these results, beta-propiolactone was extremely efficacious for the cold sterilization of non-A/non-B type 1 hepatitis virus.

Inactivation of non-A, non-B virus infectivity by a beta propiolactone/ultraviolet irradiation treatment and Aerosil adsorption procedure used for preparation of a stabilized human serum.

Inoculation of chimpanzees revealed that starting material for the preparation of a pooled stabilized human serum preparation was contaminated with non-A, non-B hepatitis virus(es). This material was subjected to beta-propiolactone/ultraviolet irradiation treatment and adsorption with an insolubilized silicic acid under conditions employed for sterilization of the final product (Biseko, Biotest). The treated material did not transmit hepatitis to 2 inoculated chimpanzees. These animals were subsequently found to be susceptible to non-A, non-B infection by challenge with the untreated material. These findings demonstrate a non-A, non-B type hepatitis virus to be susceptible to inactivation by the methods employed for sterilization of this stabilized human serum preparation.

High dose gammaglobulin therapy in adults with idiopathic thrombocytopenic purpura (ITP). Clinical effects.

This study of the effect of high-dose intravenous gammaglobulins with one or two courses of therapy in 18 adults with idiopathic thrombocytopenia purpura showed a platelet rise in thirteen patients. The highest response rates were seen in splenectomized adults. In chronic patients the response was transient only. If therapy was effective, increased values of platelet-associated IgG were reduced, while shortened platelet survival times were prolonged. There was no influence of high-dose gammaglobulins on platelet function. different 7S-preparations such as beta-propiolactone modified Ig, pH 4 treated Ig and reduced and alkylated Ig have comparable effects.

Evaluation of the effect of betapropiolactone/ultraviolet irradiation (BPL/UV) treatment of source plasma on hepatitis transmission by factor IX complex in chimpanzees.

To evaluate the safety of a beta-Propiolactone/Ultraviolet (BPL/UV), irradiated Factor IX complex preparation we inoculated 8 chimpanzees with 25 units Factor IX/Kilo from a pool of 5 production lots which had been treated in this manner. These lots were derived from approximately 1,000 donors. Animals were followed with weekly tests for hepatitis B serologic markers and transaminases, and biweekly liver biopsies, for 6 months. No evidence of transmission of hepatitis B, or non-A, non-B viruses was observed. To further evaluate the BPL/UV procedure a plasma pool was intentionally contaminated with hepatitis B virus and one half of the pool treated with BPL/UV. Factor IX complex was isolated from the treated and untreated pools and each was inoculated into 4 chimpanzees. The Factor IX derived from untreated plasma infected all four animals with an average incubation period of 10.5 weeks, whereas that prepared from PBL/UV treated plasma infected only one of four animals with an incubation period of 21 weeks. These results were interpreted as suggesting that BPL/UV can inactivate approximately 99.9% of hepatitis B virus infectivity.