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Prophylaxis prevents joint and other bleeding episodes in patients with haemophilia A. Development of new factor concentrates with longer circulating half-lives may encourage patients to start, continue or resume prophylaxis. The aim of this study was to compare the pharmacodynamic effect of a PEGylated full-length recombinant factor VIII ( rFVIII) concentrate with that of an unmodified rFVIII concentrate with respect to the duration of prophylactic efficacy in a murine model of haemophilic joint bleeding. Mice were pretreated with BAX 855 or unmodified rFVIII at specified times before right knee puncture to induce haemarthrosis; left knee joints served as controls. Joint bleeding was evaluated using a combination of visual and histological assessments. Administration of a single dose of unmodified rFVIII before joint puncture prevented haemarthrosis in mice up to 24 h, whereas pretreatment with BAX 855 protected the joint from bleeding up to 48 h. This pharmacodynamic study showed prolonged efficacy of BAX 855 compared to ADVATE in a haemophilia A mouse joint bleeding model. This finding supports the possibility of using BAX 855 to increase FVIII trough levels and/or extend the dosing interval in patients with haemophilia A on prophylaxis, which may potentially improve prophylactic efficacy and long-term adherence. [ABSTRACT FROM AUTHOR]

Recombinant vaccinia viruses based on the highly attenuated Modified Vaccinia Ankara (MVA) strain expressing HIV-1 antigen genes were constructed by a novel procedure involving the transient use of two marker genes. The selectable markers used, the Escherichia coli guanine phosphoribosyltransferase (gpt) and the ß-galactosidase (lacZ) genes, are not retained within the final recombinant virus. The transient marker stabilisation (TMS) procedure allows the generation of marker-free recombinant viruses in a series of simple plaque purification steps. HIV-l gag pol genes were inserted into two loci of vaccinia MVA demonstrating the efficiency of the procedure. [ABSTRACT FROM AUTHOR]

Fowlpox virus (FPV) insertion plasmids were constructed that, upon integration into the viral genome via in-vivo recombination, inactivate the viral thymidine kinase ( tk) gene. Using this approach, no wild-type virus-free stocks of recombinant virus could be obtained. In contrast, either integration of foreign genes into the intergenic region of the intact FPV tk gene and the open reading frame located downstream, or the functional substitution of the inactivated FPV tk gene by an intact vaccinia virus tk gene resulted in the predicted stable recombinants that were free of wild-type virus. Our results suggest that in already highly attenuated poxvirus strains an intact tk gene is essential for efficient growth of the virus in cell culture. [ABSTRACT FROM AUTHOR]

The highly attenuated 'modified vaccinia Ankara' (MVA) strain is a potential live vaccine vector. Insertional inactivation of the tk-gene resulted in viruses difficult to purify. Co-integration of a functional fowlpox virus tk-gene allowed easy generation of recombinants, indicating that the genetically stable tk-gene region is a suitable insertion site, if tk-gene activity is substituted. [ABSTRACT FROM AUTHOR]