Neutralisation of adeno-associated virus transduction by human vitreous humour

Sławomir Andrzejewski, Peter M. Moyle, Brett W. Stringer, Jason C. Steel, Christopher J. Layton

Research output: Contribution to journalArticlepeer-review

6 Citations (Scopus)


Neutralising antibodies (NAbs), caused by past adeno-associated virus (AAV) infection, represent a critical challenge for AAV-mediated gene therapy, with even low NAb titres capable of inhibiting gene transfer, however in protein-rich environments such as the vitreous it is expected that other constituents could also interact with the transduction process. Inhibition of AAV2/2, AAV2/5, AAV2/6 and AAV2/8 transduction by human vitreous humour (VH) obtained from 80 post-mortem eye cups was investigated in this report, with clinically relevant vitreous dilutions as low as 1:2. Unexpectedly, the highest prevalence of inhibition of transduction was observed against AAV2/6, with 66% of tested samples displaying neutralisation at a 1:2 VH dilution. Only two samples showed inhibition of AAV2/8, indicating this serotype is an attractive vector for use in non-vitrectomised eyes of unscreened individuals. Levels of anti-AAV NAbs observed in the VH were much lower than previously observed in serum of a similar Australian population. Among ten tested eye cup pairs, we observed only small variation in anti-AAV NAbs levels between the left and right eye cups. Interaction with 1:2 diluted VH had an augmentation effect on AAV2/8 transduction (p = 0.004), a phenomenon which was not due to albumin or transferrin and which, if developed, might benefit the use of AAV2/8 in clinical settings.

Original languageEnglish
Pages (from-to)242-255
Number of pages14
JournalGene Therapy
Issue number5
Early online date15 Jun 2020
Publication statusPublished - May 2021
Externally publishedYes


  • Adaptive immunity
  • Gene therapy
  • Genetic vectors
  • Virology


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