Pre-existing immunity against Ad vectors

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Pre-existing immunity against Ad vectors

Pre-existing immunity against human adenovirus (HAd) serotype 5 derived vector in the human population is widespread, thus hampering its clinical use. Various components of the immune system, including neutralizing antibodies (nAbs), Ad specific T cells and type I IFN activated NK cells, contribute to dampening the efficacy of Ad vectors in individuals with pre-existing Ad immunity. In order to...

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Pre-existing immunity against vaccine vectors – friend or foe?

Over the last century, the successful attenuation of multiple bacterial and viral pathogens has led to an effective, robust and safe form of vaccination. Recently, these vaccines have been evaluated as delivery vectors for heterologous antigens, as a means of simultaneous vaccination against two pathogens. The general consensus from published studies is that these vaccine vectors have the poten...

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Proteasome Inhibition Is Partially Effective in Attenuating Pre-Existing Immunity against Recombinant Adeno-Associated Viral Vectors

Pre-existing immunity against adeno-associated virus (AAV) remains a major challenge facing the clinical use of systemic administration of recombinant AAV vectors for the treatment of genetic and acquired diseases using gene therapy. In this study, we evaluated the potential of bortezomib (marketed under trade name Velcade) to abrogate a pre-existing immunity to AAV in mice, thereby allowing su...

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Liver gene therapy by lentiviral vectors reverses anti-factor IX pre-existing immunity in haemophilic mice

A major complication of factor replacement therapy for haemophilia is the development of anti-factor neutralizing antibodies (inhibitors). Here we show that liver gene therapy by lentiviral vectors (LVs) expressing factor IX (FIX) strongly reduces pre-existing anti-FIX antibodies and eradicates FIX inhibitors in haemophilia B mice. Concomitantly, plasma FIX levels and clotting activity rose to ...

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Enhancing the Clinical Potential of AAV Vectors by Capsid Engineering to Evade Pre-Existing Immunity

Vectors based on adeno-associated viruses (AAV) have shown considerable promise in both preclinical models and increasingly in clinical trials. However, one formidable challenge is pre-existing immunity due to widespread exposure to numerous AAV variants and serotypes within the human population, which affect efficacy of clinical trials due to the accompanying high levels of anti-capsid neutral...

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ژورنال

عنوان ژورنال: Human Vaccines & Immunotherapeutics

سال: 2014

ISSN: 2164-5515,2164-554X

DOI: 10.4161/hv.29594