Residual risk of transfusion-associated infectious disease persists despite improved donor testing. Donor testing cannot protect prospectively against new viruses which may enter the population, such as HIV in 1979.Solvent- detergent treatment, introduced for plasma and plasma-fractions, is only effective against enveloped viruses (env-V). The overall program objective is to develop effective and practical decontamination processes for non-cellular transfusion products, including recombinant biologicals, which are effective against env-V and non-enveloped viruses (non-env-V), such as hepatitis A virus (HAV) and parvovirus B19 (PVB19). The goal of this application is to develop psoralen (Ps)-mediated photochemical decontamination (PCD) methods effective against at least 10(6)/ml non-env-V and env-V in non-cellular therapeutic biologicals. This goal will be achieved through the following specific aims: 1) to develop methods using a novel Ps derivative (S-59) plus ultraviolet light (UVA/UBV) to inactivate significant viral non-env-V and env-V pathogens; 2) to test further novel Ps that enhance nucleic acid inactivation specificity and efficacy for non-env-V while reducing mutagenicity using structure function matrices developed for Ps derivatives based on inactivation of env-V pathogens as the primary determinant of function; 3) to develop an ultrasonic flow system to facilitate Ps mediated inactivation on non- env-V.Efficacy will be evaluated using HAV and poliovirus, both characterized by impenetrable outer capsid structures; and 4) to utilize microwave radiation (MR) and temperature to enhance Ps-UVA viral inactivation. Efficacy will be evaluated initially using bacteriophage X 174 as a model non-decontaminate recombinant human proteins, e.g., Factor VIII. Inactivation of non-env-V and env-V pathogens will be studied using high-intensity UVA in a flow system under reduced ambient 02. The effects on protein yield, function, structure, and neo- antigenicity will be evaluated using coagulation assays, radiolabel incorporation, mass spectroscopy, and an immune tolerance assay.

Agency
National Institute of Health (NIH)
Institute
National Heart, Lung, and Blood Institute (NHLBI)
Type
Research Project (R01)
Project #
5R01HL053357-04
Application #
2519445
Study Section
Special Emphasis Panel (ZHL1-CSR-S (S1))
Project Start
1994-09-30
Project End
1999-08-31
Budget Start
1997-09-01
Budget End
1998-08-31
Support Year
4
Fiscal Year
1997
Total Cost
Indirect Cost
Name
Cerus Corporation
Department
Type
DUNS #
858999485
City
Concord
State
CA
Country
United States
Zip Code
94520