Immunogenicity of novel recombinant human activated factor VII analogues on factor VII neonatally-tolerized rats
| Autor: | Peer Norbert Jørgensen, Christian Sommer, Jes Thorn Clausen, Zaki Salanti, Lisbeth Bjerring Jensen |
|---|---|
| Rok vydání: | 2007 |
| Předmět: |
medicine.medical_specialty
Freund's Adjuvant Enzyme-Linked Immunosorbent Assay Factor VIIa Haemophilia Immune tolerance law.invention Cohort Studies chemistry.chemical_compound Immune system law Internal medicine Activated factor VII Immune Tolerance medicine Animals Humans Rats Wistar Binding Sites Factor VII business.industry Immunogenicity Thrombosis Hematology medicine.disease Recombinant Proteins Rats Endocrinology Animals Newborn chemistry Immune System Cohort Recombinant DNA business |
| Zdroj: | Thrombosis and Haemostasis. 98:721-725 |
| ISSN: | 2567-689X 0340-6245 |
| Popis: | SummaryRecombinant activated factorVII (rFVIIa; NovoSeven®) has been widely used to treat bleeding in patients with haemophilia with inhibitors. To increase the intrinsic activity, analogues of rFVIIa (rFVIIaQ, rFVIIaDVQ, and rFVIIaDVQA) with altered amino acid sequence at or near the active centre have been developed. The immunogenicity of these analogues was tested in a rat immune tolerance model.Neonatal rats received rFVIIa intraperitoneally on post-natal Day 1 and were subsequently challenged with rFVIIa in Freunds Incomplete Adjuvant subcutaneously on Days 10 and 24. Rats were tested for tolerance on Day 32; the tolerant cohort and a parallel cohort of untreated control rats were challenged with rFVIIa, rFVIIaQ, rFVIIaDVQ, or rFVIIaDVQA on Days 46 and 76. Immune responses determined by enzymelinked immunosorbent assay (ELISA) on Day 84 showed no statistically significant difference between the responses in the four control cohorts. Immune responses were higher in the control than in the tolerant cohort. Compared with rFVIIa (4/16), there was no difference in the proportion of rats that broke tolerance following challenge with rFVIIaDVQ (3/16) and rFVIIaDVQA (7/16), whereas a statistically significant greater proportion broke tolerance after challenge with rFVIIaQ (11/16). Therefore, in this model rFVIIaDVQ or rFVIIa DVQA were not more immunogenic than rFVIIa. |
| Databáze: | OpenAIRE |
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