Adenovirus‐associated antibodies in UK cohort of hemophilia patients: A seroprevalence study of the presence of adenovirus‐associated virus vector–serotypes AAV 5 and AAV 8 neutralizing activity and antibodies in patients with hemophilia A

Abstract Background Current treatment for severe hemophilia A is replacement of deficient factor. Although replacement therapy has improved life expectancy and quality, limitations include frequent infusions and high costs. Gene therapy is a potential alternative that utilizes an adeno‐associated virus ( AAV ) vector containing the human genetic code for factor 8 ( FVIII ) that transduces the liver, enabling endogenous production of FVIII . Individuals with preexisting immunity to AAV serotypes may be less likely to benefit from this treatment. Objectives This study measured seroprevalence of antibodies to AAV 5 and 8 in an UK adult hemophilia A cohort. Patients/Methods Patients were recruited from seven hemophilia centres in the UK . Citrated plasma samples from 100 patients were tested for preexisting activities against AAV 5 and 8 using AAV transduction inhibition and total antibodies assays. Results Twent‐one percent of patients had antibodies against AAV 5 and 23% had antibodies against AAV 8. Twenty‐five percent and 38% of patients exhibited inhibitors of AAV 5 or AAV 8 cellular transduction respectively. Overall seroprevalence using either assay against AAV 5 was 30% and against AAV 8 was 40% in this cohort of hemophilia A patients. Seropositivity for both AAV 5 and AAV 8 was seen in 24% of participants. Conclusions Screening for preexisting immunity may be important in identifying patients most likely to benefit from gene therapy. Clinical studies may be needed to evaluate the impact of preexisting immunity on the safety and efficacy of AAV mediated gene therapy.