Effect of route of administration of human recombinant factor VIII on its immunogenicity in Hemophilia A mice.
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.
Peng
Aaron
A
Department of Pharmaceutical Sciences, University at Buffalo, The State University of New York, 521 Hochstetter Hall, Amherst, New York 14260, USA.
Gaitonde
Puneet
P
Kosloski
Matthew P
MP
Miclea
Razvan D
RD
Varma
Prashant
P
Balu-Iyer
Sathy V
SV
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
D000906:Antibodies; D019138:Antibodies, Blocking; C078147:F8 protein, human; D005169:Factor VIII