title: Effect of route of administration of human recombinant factor VIII on its immunogenicity in Hemophilia A mice.
abstract: Factor VIII is a multi-domain glycoprotein and is an essential cofactor in the blood coagulation cascade. Its deficiency or dysfunction causes Hemophilia A, a bleeding disorder. Replacement using exogenous recombinant Factor VIII (FVIII) is the first line of therapy for Hemophilia A. Immunogenicity, the development of binding (total) and neutralizing (inhibitory) antibody against administered protein is a clinical complication of the therapy. There are several product related factors such as presence of aggregates, route and frequency of administration and glycosylation have been shown to contribute to immunogenicity. The effect of route of administration of FVIII on antibody development in Hemophilia A is not completely understood. Here we investigated the effect of route of administration (s.c. or i.v.) on immunogenicity in Hemophilia A mice. The total and inhibitory titers were determined using ELISA and modified Bethesda Assay respectively. The results indicated that s.c. is more immunogenic compared to i.v. route in terms of total antibody titer development (binding antibodies) but no significant differences in inhibitory titer levels could be established.
authors.affiliation: Department of Pharmaceutical Sciences, University at Buffalo, The State University of New York, 521 Hochstetter Hall, Amherst, New York 14260, USA.
authors.forename: Aaron
authors.initials: A
authors.lastname: Peng
authors.forename: Puneet
authors.initials: P
authors.lastname: Gaitonde
authors.forename: Matthew P
authors.initials: MP
authors.lastname: Kosloski
authors.forename: Razvan D
authors.initials: RD
authors.lastname: Miclea
authors.forename: Prashant
authors.initials: P
authors.lastname: Varma
authors.forename: Sathy V
authors.initials: SV
authors.lastname: Balu-Iyer
mesh_terms: D000818:Animals; D000906:Antibodies / Q000032:analysis; D019138:Antibodies, Blocking / Q000494:pharmacology; D016466:CHO Cells; D006224:Cricetinae; D003412:Cricetulus; D004797:Enzyme-Linked Immunosorbent Assay; D005169:Factor VIII / Q000008:administration & dosage* / Q000276:immunology* / Q000494:pharmacology; D006031:Glycosylation; D006467:Hemophilia A / Q000188:drug therapy / Q000378:metabolism*; D006801:Humans; D007275:Injections, Intravenous; D007279:Injections, Subcutaneous; D051379:Mice
chemical_list: D000906:Antibodies; D019138:Antibodies, Blocking; C078147:F8 protein, human; D005169:Factor VIII