ArticleInvestigative ophthalmology & visual science2025
Investigating the Immunogenic Potential of Variations in Host Cell Protein Levels in Clinical-Grade AAV8 Products.
Article in Investigative ophthalmology & visual science, 2025. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 5 papers.
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Who cites it
5 citing papers in PubMed.
- Impact of downstream purification process and AAV serotype on protein-impurity clearance.Molecular therapy. Advances · 2026Article
- Host cell protein impurities in therapeutic proteins: overview of advances in detection, nonconventional removal technologies and immunogenicity assessment.Journal of biological engineering · 2026Review
- Downstream Purification Strategies for Virus-like Particles: A Systematic Review of Structure Preservation, Impurity Control, and Viral Safety.Microorganisms · 2026Review
- Challenges and Opportunities in Lentivirus Viral Vector Manufacturing for In Vivo Applications.Biomedicines · 2026Review
- Characterization of difficult-to-remove host cell proteins in adeno-associated virus downstream processing.Molecular therapy. Methods & clinical development · 2025Article
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Authors and funding
12 authors.
Funding
No grant is acknowledged in the PubMed record.
Abstract
Purpose: Adeno-associated virus (AAV) formulations for gene therapy contain manufacturing-associated impurities such as residual host cell protein (HCP). The aim of this study was to investigate whether high levels of HCP in AAV formulations are associated with increased inflammation and reduced ocular tolerability. Methods: Three lots of clinical-grade AAV8 vector were analyzed for the presence of manufacturing-associated impurities. The HCP component of these impurities was characterized using mass spectrometry. Lots were then compared regarding their capacity to induce a cytokine response in primary human plasmacytoid dendritic cells (pDCs) and THP-1 cells. Furthermore, the results of an ocular safety study in healthy nonhuman primates were analyzed post hoc to investigate the influence of HCP levels on clinical signs of inflammation and chorioretinal atrophy (CRA) development. Results: Vector lots displayed up to a ∼40-fold variation in HCP levels. Human galactin-3-binding protein was the only major HCP contaminant. Stimulation of human pDCs and THP-1 cells with a high HCP lot did not result in an increased cytokine response. High HCP also did not exacerbate clinical signs of inflammation. However, on retinal imaging, CRA lesions were significantly larger in high HCP-treated eyes (P = 0.001-0.048). Conclusions: HCP impurities were of low complexity, but pronounced variations in their abundance were observed between lots. High HCP levels were not overtly immunogenic in vivo and in vitro. However, despite statistical limitations, they seemed to be associated with increased CRA. Thus, a negative effect of high HCP levels on retinal tolerability could not be ruled out.
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