ArticleJournal of pharmaceutical sciences2012
Native-like aggregates of factor VIII are immunogenic in von Willebrand factor deficient and hemophilia a mice.
Article in Journal of pharmaceutical sciences, 2012. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 19 papers.
What it found
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The abstract states no effect estimate the extractor could read, or names no intervention and outcome on the map, so this paper lights no cell and moves no belief. It is still indexed, cited and linked below.
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Trials whose registry record cites this paper, or whose number appears in the abstract. A trial that started after this paper was published is citing it as background, not reporting it.
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Who cites it
19 citing papers in PubMed, 49 citations in OpenAlex.
- A Deletion Variant of Human Factor VIII Displaying Low Immunogenicity in a Murine Model of Hemophilia A.International journal of molecular sciences · 2025Article
- Highly variable aggregation and glycosylation profiles and their roles in immunogenicity to protein-based therapeutics.Journal of pharmaceutical sciences · 2025Review
- Pharmaceutical Aspects and Clinical Evaluation of COVID-19 Vaccines.Immunological investigations · 2021Review
- Immunogenicity Challenges Associated with Subcutaneous Delivery of Therapeutic Proteins.BioDrugs : clinical immunotherapeutics, biopharmaceuticals and gene therapy · 2021Review
- Sedimentation Velocity Analytical Ultracentrifugation of Oxidized Recombinant Full-Length Factor VIII.Frontiers in immunology · 2020Article
- Immune Responses to Plasma-Derived Versus Recombinant FVIII Products.Frontiers in immunology · 2020Review
- Immunogenicity of Bioproducts: Cellular Models to Evaluate the Impact of Therapeutic Antibody Aggregates.Frontiers in immunology · 2020Review
- Immunogenicity of Protein Pharmaceuticals.Journal of pharmaceutical sciences · 2019Review
- How Full-Length FVIII Benefits from Its Heterogeneity - Insights into the Role of the B-Domain.Pharmaceutical research · 2019Article
- N-linked glycosylation modulates the immunogenicity of recombinant human factor VIII in hemophilia A mice.Haematologica · 2018Article
- Protein Nanoparticles Promote Microparticle Formation in Intravenous Immunoglobulin Solutions During Freeze-Thawing and Agitation Stresses.Journal of pharmaceutical sciences · 2018Article
- Challenges and Opportunities for the Subcutaneous Delivery of Therapeutic Proteins.Journal of pharmaceutical sciences · 2018Review
- Microparticles and Nanoparticles Delivered in Intravenous Saline and in an Intravenous Solution of a Therapeutic Antibody Product.Journal of pharmaceutical sciences · 2017Article
- Physical Characterization and Innate Immunogenicity of Aggregated Intravenous Immunoglobulin (IGIV) in an In Vitro Cell-Based Model.Pharmaceutical research · 2016Article
- Mouse Models for Assessing Protein Immunogenicity: Lessons and Challenges.Journal of pharmaceutical sciences · 2016Review
- Soy phosphatidylinositol containing nanoparticle prolongs hemostatic activity of B-domain deleted factor VIII in hemophilia A mice.Journal of pharmaceutical sciences · 2015Article
- The Role of Aggregates of Therapeutic Protein Products in Immunogenicity: An Evaluation by Mathematical Modeling.Journal of immunology research · 2015Article
- Effects of replacement of factor VIII amino acids Asp519 and Glu665 with Val on plasma survival and efficacy in vivo.The AAPS journal · 2014Article
- Immunogenicity of subcutaneously administered therapeutic proteins--a mechanistic perspective.The AAPS journal · 2013Review
Corrections and comments
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Authors and funding
5 authors at 2 institutions in 1 country.
Funding
Abstract
The administration of recombinant factor VIII (FVIII) is the first-line therapy for hemophilia A (HA), but 25%-35% of patients develop an inhibitory antibody response. In general, the presence of aggregates contributes to unwanted immunogenic responses against therapeutic proteins. FVIII has been shown to form both native-like and nonnative aggregates. Previously, we showed that nonnative aggregates of FVIII are less immunogenic than the native protein. Here, we investigated the effect of native-like aggregates of FVIII on immunogenicity in HA and von Willebrand factor knockout (vWF(-/-)) mice. Mice immunized with native-like aggregates showed significantly higher inhibitory antibody titers than animals that received native FVIII. Following restimulation in vitro with native FVIII, the activation of CD4+ T-cells isolated from mice immunized with native-like aggregates is approximately fourfold higher than mice immunized with the native protein. Furthermore, this is associated with increases in the secretion of proinflammatory cytokines IL-6 and IL-17 in the native-like aggregate treatment group. The results indicate that the native-like aggregates of FVIII are more immunogenic than native FVIII for both the B-cell and the T-cell responses.
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Registered trials
Read under generation 80e0d062 · epoch 390. Bibliography from PubMed, PubMed Central and OpenAlex; grants from NIH RePORTER; trial links from ClinicalTrials.gov; estimates, votes and beliefs from the OpenQuestion graph.