AAE8 Antibody

Overview of AAV8 Antibodies

AAV8 antibodies are immunoglobulins that recognize and neutralize AAV8 capsid proteins. These antibodies arise from prior exposure to wild-type AAV8 or cross-reactive immune responses, posing challenges for AAV8-based gene therapies in hemophilia and other diseases .

• Structure: AAV8 antibodies typically target conformational epitopes on the viral capsid, involving interactions with complementarity-determining regions (CDRs) of the antibody paratope .

• Function: Neutralizing antibodies (NAbs) block AAV8 vector transduction by preventing viral attachment or entry into host cells .

Prevalence and Persistence of AAV8 Antibodies

A multicenter longitudinal study (2019–2023) evaluated AAV8 immunity in 1,036 participants with hemophilia :

Key Findings:

• AAV8 NAbs and IgG binding antibodies (BAbs) persisted at stable rates over three years .

• Co-prevalence of NAbs and BAbs was observed in 38.7% of participants, complicating eligibility for gene therapies .

Humoral Immunity Assays

• Neutralization Assay: Measures NAb titers via inhibition of AAV8 transduction in cell cultures .

• ELISA: Quantifies IgG/IgM BAbs using immobilized AAV8 capsids .

Cell-Mediated Immunity Assays

• ELISpot: Detects interferon-γ secretion by T cells exposed to AAV8 peptide pools .

Gene Therapy Barriers

• Pre-existing Immunity: 46.9% of hemophilia patients had baseline NAbs against AAV8, excluding them from treatment .

• Immunogenicity Risks: AAV8 antibodies correlate with reduced therapeutic efficacy and adverse immune reactions .

Mitigation Strategies

• Plasmapheresis: Temporarily reduces NAb titers .

• Capsid Engineering: Modifying AAV8 epitopes to evade antibody recognition .

Research Gaps and Future Directions

• Epitope Diversity: Limited structural data on AAV8-specific paratopes .

• Cross-Reactivity: Mechanisms of antibody cross-reactivity between AAV serotypes remain poorly understood .

• Biomarker Development: Predictive models for immunogenicity risk are needed .

Data Sources and Validation

Studies cited here derive from peer-reviewed methodologies, including:

• Multicenter Trials: Rigorous longitudinal designs with standardized assays .

• Structural Biology: High-resolution techniques (e.g., cryo-EM) for epitope characterization .