September 2016
Volume 57, Issue 12
Open Access
ARVO Annual Meeting Abstract  |   September 2016
Humoral immune response to subretinal AAV8 in non-human primates
Author Affiliations & Notes
  • Felix Friedrich Reichel
    University Eye Hospital Tübingen, Tübingen, BW, Germany
    Institute for Ophthalmic Research, Centre for Ophthalmology, University of Tübingen, Tübingen, Germany
  • Tobias Peters
    STZ eye trial at the Center for Ophthalmology, University of Tübingen, Tübingen, Germany
  • Regine Muehlfriedel
    Institute for Ophthalmic Research, Centre for Ophthalmology, University of Tübingen, Tübingen, Germany
  • Martin Biel
    Center for Integrated Protein Science Munich (CIPSM) at the Department of Pharmacy - Center for Drug Research, Ludwig-Maximilians-Universität München, Munich, Germany
  • Francois Paquet-Durand
    Institute for Ophthalmic Research, Centre for Ophthalmology, University of Tübingen, Tübingen, Germany
  • Marius Ueffing
    Institute for Ophthalmic Research, Centre for Ophthalmology, University of Tübingen, Tübingen, Germany
  • Bernd Wissinger
    Institute for Ophthalmic Research, Centre for Ophthalmology, University of Tübingen, Tübingen, Germany
  • Karl Ulrich Bartz-Schmidt
    University Eye Hospital Tübingen, Tübingen, BW, Germany
    Institute for Ophthalmic Research, Centre for Ophthalmology, University of Tübingen, Tübingen, Germany
  • M. Dominik Fischer
    University Eye Hospital Tübingen, Tübingen, BW, Germany
    Institute for Ophthalmic Research, Centre for Ophthalmology, University of Tübingen, Tübingen, Germany
  • Stylianos Michalakis
    Center for Integrated Protein Science Munich (CIPSM) at the Department of Pharmacy - Center for Drug Research, Ludwig-Maximilians-Universität München, Munich, Germany
  • Footnotes
    Commercial Relationships   Felix Reichel, None; Tobias Peters, None; Regine Muehlfriedel, None; Martin Biel, None; Francois Paquet-Durand, None; Marius Ueffing, None; Bernd Wissinger, None; Karl Ulrich Bartz-Schmidt, None; M. Dominik Fischer, None; Stylianos Michalakis, None
  • Footnotes
    Support  Tistou & Charlotte Kerstan Stiftung
Investigative Ophthalmology & Visual Science September 2016, Vol.57, 778. doi:
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      Felix Friedrich Reichel, Tobias Peters, Regine Muehlfriedel, Martin Biel, Francois Paquet-Durand, Marius Ueffing, Bernd Wissinger, Karl Ulrich Bartz-Schmidt, M. Dominik Fischer, Stylianos Michalakis; Humoral immune response to subretinal AAV8 in non-human primates. Invest. Ophthalmol. Vis. Sci. 2016;57(12):778.

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      © ARVO (1962-2015); The Authors (2016-present)

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Abstract

Purpose : Knowledge of the humoral immune response to single subretinal administration of clinical grade recombinant adeno-associated virus (rAAV) in non-human primates is a key factor for the development of safe and efficient clinical trial protocols for retinal gene therapy. This study investigated longitudinal changes of anti-drug-antibody (ADA) titres in non-human primates (NHPs, Macacca fascicularis) between before and after single administration of rAAV8-pseudotyped virus.

Methods : 18 NHPs received subretinal injections in three cohorts (high dose: 1x1012 vector genomes [vg], low dose: 1x1011 vg, or vehicle only) and concomitant immunosuppressive therapy equivalent to a clinical trial scenario. Four additional animals received intravitreal injections to mimic via falsa application. Baseline samples were compared to those taken 1, 2 and 3 days and 1, 4 and 13 weeks after application of the vector. A sandwich-ELISA was developed and used to quantify ADAs directed against the rAAV8 capsid

Results : ADA titres in all animals of the high dose group stayed constant over the 13-week observation period. Variability was greater in the low dose and the intravitreal control cohort. Mean titres pre- and 4 weeks post-treatment were 50.82 ± 35.67 (mean ± sd) and 47.70 ± 30.24 in all animals receiving vector. The mean titres of low and high dose group did not vary from the ones of the control group, which had received only saline injections.

Conclusions : This study provides data relevant for clinical retinal gene therapy trials, where rAAV8 might be used for subretinal delivery of therapeutic transgenes. When mimicking the clinical scenario with clinical grade vector, surgery and concomitant immunosuppression, no induction of anti-drug-antibodies occurred in non-human primates.

This is an abstract that was submitted for the 2016 ARVO Annual Meeting, held in Seattle, Wash., May 1-5, 2016.

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