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Adeno-associated virus neutralising antibodies in type 1 diabetes mellitus

Gene Therapy volume 26, pages 250–263 (2019)Cite this article

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Abstract

Recombinant Adeno-associated viruses (AAVs) are an attractive vector for gene therapy delivery which may be blocked by AAV neutralising antibodies (NAbs). As Type 1 Diabetes (T1DM) is an endocrine disease of immunological origin, it is likely that NAb profiles are altered in the disease. In this study NAb to AAV2, AAV5, AAV6, and AAV8 in 72 subjects with T1DM and 45 non-diabetic patients were measured over a 4-year follow-up period. AAV2 NAb titres were significantly lower in non-diabetic subjects (P = 0.036). The T1DM group had more AAV8 NAb activity at baseline (P = 0.019), whilst after 4 years follow-up the T1DM group displayed developed increased AAV 5 (P = 0.03), 6 (P = 0.03) and 8 (P = 0.002) activity relative to the control group, however, overall AAV5 and 8 NAb levels were very low in patients <40. AAV NAb titre activity and prevalence generally appears higher in T1DM, however, low levels of AAV 5 and 8, particular in younger adult age groups at which T1DM can be targeted, could make these attractive vectors to target the disease.

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Acknowledgements

Aparna Murali and Charmaine Ramlogan-Steel were supported by fellowships from the Layton Vision Foundation. Slawomir Andrzejewski was supported by a fellowship from the Gallipoli Medical Research Foundation. The LANDMark study was funded by the Juvenile Diabetes Research Foundation (JDRFI 8-2008-362).

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Authors and Affiliations

  1. LVF Ophthalmology Research Centre, Translational Research Institute, 37 Kent St, Woolloongabba, Brisbane, QLD, 4102, Australia

    Slawomir Andrzejewski, Aparna Murali, Charmaine Ramlogan-Steel, Jason C. Steel & Christopher J. Layton

  2. Faculty of Medicine, Greenslopes Clinical School, The University of Queensland, Newdegate St, Greenslopes, Brisbane, QLD, 4120, Australia

    Slawomir Andrzejewski, Aparna Murali & Christopher J. Layton

  3. School of Health, Medical and Applied Sciences, CQUniversity, Bruce Highway, North Rockhampton, QLD, 4702, Australia

    Charmaine Ramlogan-Steel & Jason C. Steel

  4. Institute of Health and Biomedical Innovation, Queensland University of Technology, 60 Musk Avenue, Kelvin Grove, Brisbane, QLD, 4059, Australia

    Katie P. Edwards & Nathan Efron

  5. Queensland University of Technology, Kelvin Grove, Brisbane, QLD, 4059, Australia

    Katie P. Edwards & Nathan Efron

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Andrzejewski, S., Murali, A., Ramlogan-Steel, C. et al. Adeno-associated virus neutralising antibodies in type 1 diabetes mellitus. Gene Ther 26, 250–263 (2019). https://doi.org/10.1038/s41434-019-0076-5

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