Adenovirus-associated antibodies in UK cohort of hemophilia patients: A seroprevalence study of the presence of adenovirus-associated virus vector-serotypes AAV5 and AAV8 neutralizing activity and antibodies in patients with hemophilia A.

Stanford, Sophia and Pink, Ruth and Creagh, Desmond and Clark, Amanda and Lowe, Gillian and Curry, Nicola and Pasi, John and Perry, David and Fong, Sylvia and Hayes, Gregory and Chandrakumaran, Kandiah and Rangarajan, Savita (2019) Adenovirus-associated antibodies in UK cohort of hemophilia patients: A seroprevalence study of the presence of adenovirus-associated virus vector-serotypes AAV5 and AAV8 neutralizing activity and antibodies in patients with hemophilia A. Research and practice in thrombosis and haemostasis, 3 (2). pp. 261-267. ISSN 2475-0379. This article is available to all HEFT staff and students via ASK Discovery tool http://tinyurl.com/z795c8c by using their HEFT Athens login IDs

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Official URL: http://europepmc.org/abstract/MED/31011709

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 AAV5 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 AAV5 and 8 using AAV transduction inhibition and total antibodies assays.

Results

Twent-one percent of patients had antibodies against AAV5 and 23% had antibodies against AAV8. Twenty-five percent and 38% of patients exhibited inhibitors of AAV5 or AAV8 cellular transduction respectively. Overall seroprevalence using either assay against AAV5 was 30% and against AAV8 was 40% in this cohort of hemophilia A patients. Seropositivity for both AAV5 and AAV8 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.

Item Type: Article
Additional Information: This article is available to all HEFT staff and students via ASK Discovery tool http://tinyurl.com/z795c8c by using their HEFT Athens login IDs
Subjects: QZ Pathology. Oncology
WH Haemic and lymphatic systems. Haematology
Divisions: Planned IP Care > Oncology and Clinical Haematology
Related URLs:
Depositing User: Mrs Yolande Brookes
Date Deposited: 26 Apr 2019 14:18
Last Modified: 26 Apr 2019 14:18
URI: http://www.repository.heartofengland.nhs.uk/id/eprint/2051

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