September 2016
Volume 57, Issue 12
ARVO Annual Meeting Abstract  |   September 2016
Intravitreal injection of rAAV2/2–ND4 (GS010): immune responses and ocular inflammation in non-human primates and patients with Leber Hereditary Optic Neuropathy (LHON)
Author Affiliations & Notes
  • Nitza Thomasson
    Gensight Biologics, Paris, France
  • Celine Bouquet
    Gensight Biologics, Paris, France
  • Anne Galy
    Gensight Biologics, Paris, France
  • Serge Fitoussi
    Gensight Biologics, Paris, France
  • Sandrine Meunier
    Gensight Biologics, Paris, France
  • Scott Uretsky
    Gensight Biologics, Paris, France
  • Catherine Vignal
    Centre Hospitalier National d’Ophtalmologie des Quinze-Vingts, Paris, France
  • Jose Sahel
    Centre Hospitalier National d’Ophtalmologie des Quinze-Vingts, Paris, France
  • Jean Philppe Combal
    Gensight Biologics, Paris, France
  • Footnotes
    Commercial Relationships   Nitza Thomasson, GenSight Biologics (E); Celine Bouquet, GenSight Biologics (E); Anne Galy, GenSight Biologics (E); Serge Fitoussi, GenSight Biologics (E); Sandrine Meunier, GenSight Biologics (E); Scott Uretsky, GenSight Biologics (E); Catherine Vignal, GenSight Biologics (C); Jose Sahel, GenSight Biologics (I), GenSight Biologics (C); Jean Philppe Combal, GenSight Biologics (E)
  • Footnotes
    Support  None
Investigative Ophthalmology & Visual Science September 2016, Vol.57, 1177. doi:
  • Views
  • Share
  • Tools
    • Alerts
      This feature is available to authenticated users only.
      Sign In or Create an Account ×
    • Get Citation

      Nitza Thomasson, Celine Bouquet, Anne Galy, Serge Fitoussi, Sandrine Meunier, Scott Uretsky, Catherine Vignal, Jose Sahel, Jean Philppe Combal; Intravitreal injection of rAAV2/2–ND4 (GS010): immune responses and ocular inflammation in non-human primates and patients with Leber Hereditary Optic Neuropathy (LHON). Invest. Ophthalmol. Vis. Sci. 2016;57(12):1177. doi:

      Download citation file:

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

  • Supplements

Purpose : AAV viral vectors are known to trigger host immune response which may affect safety and efficacy of gene therapies. Intravitreal injection (IVI) of GS010, a rAAV2/2-ND4 vector, is developed for treatment of vision loss in LHON-ND4 patients. We thus investigated the relationship between anti-AAV2 antibody levels and local inflammatory reactions after GS010 administration.

Methods : Non-human primates (NHP; n=3M+3F per group) and LHON-ND4 patients (Phase I/IIa; injection in the worst seeing-eye) underwent IVI of GS010 with two (4.3E11; 3.1E11 vg/eye) and four dose levels (9E9; 3E10; 9E10; 1.8E11 vg/eye; n=3 per dose + 3 at the recommended 9E10 dose) respectively. Ocular examinations were performed up to 6 months post-injection in NHP and up to 48 weeks in patients. NHP eye histopathology was performed. Serum was collected from all patients and aqueous humor samples prior to injection in the last 8 patients, for quantification of anti-AAV2 IgG by ELISA and neutralizing antibodies (NAbs) by luciferase assay on HEK 293 cells.

Results : At baseline, 55% of NHPs had undetectable NAb titers and 45% had titers of 1:5–1:400. All animals showed titer increase up to 1:12800 starting week 2 post-injection. Between 2 and 6 months titers remained stable. Ocular inflammation was observed in up to 80% of NHPs, but without deleterious effects on retinas.
Preliminary Phase I/IIa data showed that 7 out of the 15 patients had undetectable NAb levels at baseline. Two weeks after injection, IgG titers increased up to 19 times their baseline level in 7 patients and NAbs up to 39 times in 10 patients. No obvious correlation with the dose level was observed. Eleven of 15 patients experienced ocular inflammation without apparent correlation with the humoral serum response. Antibody titers and NAbs in aqueous humor at baseline are still under evaluation.

Conclusions : A humoral serum response against AAV2 was induced from 2 weeks post-IVI of GS010 in both NHP and humans. Ocular inflammations were also observed, but currently no consistent correlation with antibody levels are noted. Additional follow-up of humoral and cellular immunogenicity in upcoming nonclinical study and Phase III trials will help to confirm these observations and the potential predictable impact for contralateral eye injection.

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


This PDF is available to Subscribers Only

Sign in or purchase a subscription to access this content. ×

You must be signed into an individual account to use this feature.