The use of tri(n-butyl)phosphate detergent mixtures to inactivate hepatitis viruses and human immunodeficiency virus in plasma and plasma's subsequent fractionation.
The treatment of plasma with organic solvent/detergent mixtures at the time of plasma collection or pooling could reduce the exposure of technical staff to infectious viruses and enhance the viral safety of the final product. Treatment of plasma for 4 hours with 2-percent tri(n-butyl)phosphate (TNBP) at 37 degrees C, with 1-percent TNBP and 1-percent polyoxyethylensorbitan monooleate (Tween 80) at 30 degrees C, or with 1-percent TNBP and 1-percent polyoxyethylene ethers, (Triton X-45) at 30 degrees C resulted in the rapid and complete inactivation of greater than or equal to 10(4) tissue culture-infectious doses (TCID50) of vesicular stomatitis and Sindbis viruses, which are used as surrogates. Treatment of plasma with TNBP and TNBP and Tween-80 was shown to inactivate greater than or equal to 10(4) TCID50 of human immunodeficiency virus. TNBP treatment of plasma contaminated with 10(6) chimpanzee-infectious doses (CID50) of hepatitis B virus and 10(5) CID50 of non-A,non-B hepatitis virus prevented the transmission of hepatitis to chimpanzees. Immediately after treatment of plasma with 2-percent TNBP, the recovery of factors VIII, IX, and V and antithrombin III was 80, 90, 40, and 100 percent, respectively. Recovery of all factors was greater than or equal to 90 percent after treatment with TNBP and detergent mixtures. Treated plasma was fractionated by standard techniques into antihemophilic factor and prothrombin complex concentrates, immune globulin, and albumin. Prior treatment with TNBP or TNBP and detergent did not affect the separations of desired proteins. Therefore, it appears possible to inactivate viruses in plasma before the execution of standard fractionation procedures.(ABSTRACT TRUNCATED AT 250 WORDS)
Piët
M P
MP
New York Blood Center, New York.
Chin
S
S
Prince
A M
AM
Brotman
B
B
Cundell
A M
AM
Horowitz
B
B
D001798:Blood Proteins / Q000502:physiology; D002458:Cell Fractionation; D003902:Detergents / Q000494:pharmacology; D006678:HIV / Q000187:drug effects* / Q000502:physiology; D006518:Hepatitis Viruses / Q000187:drug effects* / Q000502:physiology; D006801:Humans; D010755:Organophosphates / Q000494:pharmacology; D009943:Organophosphorus Compounds; D010949:Plasma / Q000187:drug effects / Q000382:microbiology*; D013024:Soybean Oil / Q000494:pharmacology; D013501:Surface-Active Agents; D014775:Virus Activation / Q000187:drug effects* / Q000502:physiology
D001798:Blood Proteins; D003902:Detergents; D010755:Organophosphates; D009943:Organophosphorus Compounds; D013501:Surface-Active Agents; D013024:Soybean Oil; C009524:tributyl phosphate