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Exposure to wild-type AAV drives distinct capsid immunity profiles in humans.

A new interesting article has been published in J Clin Invest. 2018 Oct 22. pii: 122372. doi: 10.1172/JCI122372. [Epub ahead of print] and titled:

Exposure to wild-type AAV drives distinct capsid immunity profiles in humans.

Authors of this article are:

Kuranda K, Jean-Alphonse P, Leborgne C, Hardet R, Collaud F, Marmier S, Costa Verdera H, Ronzitti G, Veron P, Mingozzi F.

A summary of the article is shown below:

Recombinant adeno-associated virus (AAV) vectors have been broadly adopted as a gene delivery tool in clinical trials, owing to their high efficiency of transduction of several host tissues and their low immunogenicity. However, a considerable proportion of the population is naturally exposed to the WT virus from which AAV vectors are derived, which leads to the acquisition of immunological memory that can directly determine the outcome of gene transfer. Here, we show that prior exposure to AAV drives distinct capsid immunity profiles in healthy subjects. In peripheral blood mononuclear cells (PBMCs) isolated from AAV-seropositive donors, recombinant AAV triggered TNF-α secretion in memory CD8+ T cells, B cell differentiation into antibody-secreting cells, and anti-capsid antibody production. Conversely, PBMCs isolated from AAV-seronegative individuals appeared to carry a population of NK cells reactive to AAV. Further, we demonstrated that the AAV capsid activates IL-1β and IL-6 cytokine secretion in monocyte-related dendritic cells (moDCs). IL-1β and IL-6 blockade inhibited the anti-capsid humoral response in vitro and in vivo. These results provide insights into immune responses to AAV in humans, define a possible role for moDCs and NK cells in capsid immunity, and open new avenues for the modulation of vector immunogenicity.

Check out the article’s website on Pubmed for more information:

This article is a good source of information and a good way to become familiar with topics such as:

Gene therapy;Immunology


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