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Infusion reactions to adeno‐associated virus (AAV)-based gene therapy: Mechanisms, diagnostics, treatment and review of the literature
  • +8
  • Kin Israel Notarte,
  • Jesus Alfonso Catahay,
  • Raymart Macaset,
  • Jin Liu,
  • Jacqueline Veronica Velasco,
  • Princess Juneire Peligro,
  • Jolaine Vallo,
  • Nathaniel Goldrich,
  • Lokesh Lahoti,
  • Jiayan Zhou,
  • Brandon Henry
Kin Israel Notarte
Johns Hopkins University Department of Pathology
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Jesus Alfonso Catahay
Saint Peter’s University Hospital
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Raymart Macaset
Monmouth Medical Center
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Jin Liu
Johns Hopkins University Department of Pathology
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Jacqueline Veronica Velasco
University of Santo Tomas Faculty of Medicine and Surgery
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Princess Juneire Peligro
University of Santo Tomas Faculty of Medicine and Surgery
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Jolaine Vallo
University of Santo Tomas Faculty of Medicine and Surgery
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Nathaniel Goldrich
New York Medical College
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Lokesh Lahoti
Saint Peter’s University Hospital
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Jiayan Zhou
Stanford University Department of Medicine
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Brandon Henry
Cincinnati Children’s Hospital Medical Center

Corresponding Author:[email protected]

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Abstract

The use of adeno-associated virus (AAV) vectors in gene therapy has demonstrated great potential in treating genetic disorders. However, infusion-associated reactions (IARs) pose a significant challenge to the safety and efficacy of AAV-based gene therapy. This review provides a comprehensive summary of the current understanding of IARs to AAV therapy, including their underlying mechanisms, clinical presentation, and treatment options. Toll-like receptor activation and subsequent production of pro-inflammatory cytokines are associated with IARs, stimulating neutralizing antibodies and T-cell responses that interfere with gene therapy. Risk factors for IARs include high titers of pre-existing neutralizing antibodies, previous exposure to AAV, and specific comorbidities. Clinical presentation ranges from mild flu-like symptoms to severe anaphylaxis and can occur during or after AAV administration. There are no established guidelines for pre- and post-administration tests for AAV therapies, and routine laboratory requests are not standardized. Treatment options include corticosteroids, plasmapheresis, and supportive medications such as antihistamines and acetaminophen, but there is no consensus on the route of administration, dosage, and duration. This review highlights the inadequacy of current treatment regimens for IARs and the need for further research to improve the safety and efficacy of AAV-based gene therapy.
12 Jul 2023Submitted to Journal of Medical Virology
12 Jul 2023Submission Checks Completed
12 Jul 2023Assigned to Editor
12 Jul 2023Review(s) Completed, Editorial Evaluation Pending
17 Jul 2023Reviewer(s) Assigned
29 Aug 2023Editorial Decision: Revise Major
11 Sep 20231st Revision Received
12 Sep 2023Submission Checks Completed
12 Sep 2023Review(s) Completed, Editorial Evaluation Pending
12 Sep 2023Assigned to Editor
14 Sep 2023Reviewer(s) Assigned
01 Oct 2023Editorial Decision: Revise Minor
04 Nov 20232nd Revision Received
06 Nov 2023Assigned to Editor
06 Nov 2023Submission Checks Completed
06 Nov 2023Review(s) Completed, Editorial Evaluation Pending
14 Nov 2023Editorial Decision: Accept