Table 2 Adverse immune response against AAV in haemophilia B clinical trials
From: Improving clinical efficacy of adeno associated vectors by rational capsid bioengineering
Vector | No of subjects | Vector dose | Adverse Effect | Immune response | Reference |
|---|---|---|---|---|---|
AAV2 | 2 | 2X10^12 (high dose) | Liver toxicity based on elevated AST/ALT levels beginning 4Â weeks post vector infusion with concomitant decline of circulating h.FIX to the baseline (<0.1%) by 8Â weeks | CD8+ T cell response against AAV capsid as well as preexisting neutralizing antibody against AAV2 capsid prevented long term expression | [11] |
AAV2 | 4 | 4X10^11 (low dose) | No increase in circulating hF.IX from the baseline (<0.1%), increased transaminases only in one subject having the lowest pretreatment NAb | CD8+ T cell response against AAV capsid as well as prexisting neutralizing antibody against AAV2 capsid prevented hF.IX expression | [11] |
AAV8 | 1 | 2X10^12 (high dose) | Liver toxicity based on elevated AST/ALT levels beginning 8Â weeks post vector infusion with concomitant decline of circulating hF.IX levels | CD8+ T cell response against AAV capsid leading to destruction of the transduced hepatocytes | [16] |