[No ELISA detectable alterations in immunogenicity following dry-hear treatment (72 hours at 80 degrees C) of FANHDI].

Objective: Neoantigen formation during heat treatment (HT) of factor VIII:von Willebrand Factor (FVIII:vWF) concentrates may induce an immune response against the modified protein, which may also affect the native protein. We present a comparative in vitro study on the immunogenicity of a dual virally inactivated (solvent-detergent and 80 degrees C 72 hours) high purity FVIII:vWF concentrate (Fanhdi) versus the same product without heat treatment.

Material and methods: For this purpose rabbit antisera were prepared using both Fanhdi and the same product from which the human albumin, used as stabilizer, had been removed (these were both HT products). Also, antisera were prepared against the same products made without the dry-heat treatment step (non-HT products). Antisera were analysed by Elisa. Mixtures of antisera with increasing amounts of product (incubation-absorption in liquid phase) were assayed in plates coated with HT and non-HT products.

Results: The binding of antibodies against HT products to ELISA plates coated with HT products, could be blocked (in a saturable manner) with non-HT products, following liquid phase incubation. These results strongly suggest the absence of neonantigens. Furthermore, the binding of antibodies against non-HT products to ELISA plates coated with non-HT products, could be blocked (also in a saturable manner) with HT products. This result indicates that there is no epitope loss.

Conclusions: The data obtained in these studies suggest that the heat treatment of viral inactivation as applied in Fanhdi, does not give rise to any major alteration in immunogenicity of the product. The data from clinical and drug surveillance studies carried out with Fanhdi do not show any indication of an increase in the frequency of inhibitors.