Photochemical treatment of platelet concentrates offers the potential for reducing transfusion-related viral and bacterial diseases.

PCT with 150 microM S-59 and a 3 J/cm(2) UVA treatment does not adversely affect in vitro properties of BC PCs stored at 22 degrees C for 7 days. The PCT process inactivated bacteria and HIV-1 inoculated into the BC PCs. These results extend the earlier reported efficacy of PCT apheresis PCs to BC PCs.

No abstract

Trypanosoma cruzi, the protozoan pathogen that causes Chagas' disease, can be found in the blood of infected individuals for their entire life span. This presents a serious challenge in safeguarding blood products. Transmission of T. cruzi from blood products is a frequent occurrence in Latin America, where Chagas' disease is endemic. This study was designed to determine whether T. cruzi could be inactivated in human platelet concentrates and plasma by a photochemical treatment process with long-wavelength UV A light (UVA, 320 to 400 nm) plus the psoralen amotosalen HCl (Cerus Corporation). Units of platelet concentrates (300 ml) and plasma (300 ml) were intentionally contaminated with approximately 10 6 T. cruzi trypomastigotes, the T. cruzi form found in the bloodstream, per ml. The viability of T. cruzi after photochemical inactivation was determined by their ability to replicate in 3T3 fibroblasts. Controls, including treatment with 150 M amotosalen or 3 J/cm 2 UVA alone, did not lead to reduction of the viability of T. cruzi in plasma or platelet concentrates. However, treatment with 150 M amotosalen plus 3 J/cm 2 UVA inactivated T. cruzi to undetectable levels in plasma and platelet concentrates. This represented a >5.4-log reduction of T. cruzi in platelet concentrates and >5.0-log reduction of T. cruzi in plasma. We conclude that the amotosalen plus UVA photochemical inactivation technology is effective in inactivating high levels of protozoan pathogens, such as T. cruzi, in platelet concentrates and plasma, as has been previously shown for numerous viruses and bacteria.

Neutralizing antibody responses to human immunodeficiency virus type 1 (HIV-1) vary widely and have not been reproducibly associated with prognosis or disease progression. We have found that both low-passage clinical isolates and laboratory-adapted strains of HIV-1 have different sensitivities to neutralization by the same antiserum, depending on the host cell in which the viral stock is prepared. One such isolate (VL069) grown in H9 cells was neutralized by 20 human sera at a geometric mean titer of 1:2,047; this same isolate prepared in peripheral blood mononuclear cell (PBMC) culture was neutralized at a mean titer of < 1:10 by the same sera. Adsorption and mixing experiments indicated that neither antibody to H9 cell components nor blocking by excess viral antigen was responsible for the differences observed. This host cell effect is rapidly reversible upon passage of the virus from PBMCs to H9 cells and back into PBMCs. In contrast, the neutralization characteristics remained remarkably stable over extended culture in PBMCs. Two laboratory strains and five clinical isolates were evaluated in expanded studies of this phenomenon. While the neutralization characteristics of most of the strains studied were affected by the host cell in which the strain was propagated, two of the strains (one clinical isolate and one laboratory strain) appeared antigenically unaffected by their cell of origin. Host cell effect was also evident in neutralization by monoclonal antibodies directed against the CD4-binding region and the V2, V3, and gp41 regions. Possible mechanisms for this host cell effect include (i) mutation during passaging; (ii) selection in different host cells of different subpopulations of the (uncloned) viral stock; and (iii) cell-specific posttranslational modifications. To explore these possibilities, the V3 through V5 region of gp120 was sequenced in preparations made by passing VL069 into H9 cells and into PBMCs; HIVMN grown in CEM-SS cells and in PBMCs was also sequenced. In both cases, a few amino acid changes outside the V3 region were found. Studies are currently under way to assess the significance of these changes.