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AAV-mediated delivery of optogenetic constructs to the macaque brain triggers humoral immune responses

Mendoza, Skyler D. and El-Shamayleh, Yasmine and Horwitz, Gregory D. (2017) AAV-mediated delivery of optogenetic constructs to the macaque brain triggers humoral immune responses. Journal of Neurophysiology, 117 (5). pp. 2004-2013. ISSN 0022-3077. PMCID PMC5411474. doi:10.1152/jn.00780.2016.

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Gene delivery to the primate central nervous system via recombinant adeno-associated viral vectors (AAV) allows neurophysiologists to control and observe neural activity precisely. A current limitation of this approach is variability in vector transduction efficiency. Low levels of transduction can foil experimental manipulations, prompting vector readministration. The ability to make multiple vector injections into the same animal, even in cases where successful vector transduction has already been achieved, is also desirable. However, vector readministration has consequences for humoral immunity and gene delivery that depend on vector dosage and route of administration in complex ways. As part of optogenetic experiments in rhesus monkeys, we analyzed blood sera collected before and after AAV injections into the brain and quantified neutralizing antibodies to AAV using an in vitro assay. We found that injections of AAV1 and AAV9 vectors elevated neutralizing antibody titers consistently. These immune responses were specific to the serotype injected and were long lasting. These results demonstrate that optogenetic manipulations in monkeys trigger immune responses to AAV capsids, suggesting that vector readministration may have a higher likelihood of success by avoiding serotypes injected previously.

Item Type:Article
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URLURL TypeDescription CentralArticle
Horwitz, Gregory D.0000-0001-5130-5259
Additional Information:© 2016 Journal of Neurophysiology. Submitted 28 September 2016; accepted in final form 10 February 2017. This work was supported by National Institutes of Health Grants EY-024362 and OD-010425. No conflicts of interest, financial or otherwise, are declared by the authors. Author Contributions: S.D.M. and Y.E.-S. performed experiments; S.D.M. and Y.E.-S. analyzed data; S.D.M., Y.E.-S., and G.D.H. interpreted results of experiments; S.D.M. and Y.E.-S. prepared figures; S.D.M., Y.E.-S., and G.D.H. drafted manuscript; S.D.M., Y.E.-S., and G.D.H. edited and revised manuscript; S.D.M., Y.E.-S., and G.D.H. approved final version of manuscript. We thank the veterinary staff at the Washington National Primate Center for assistance with blood serum collection and Donna Prunkard at the University of Washington Department of Pathology Flow Cytometry Core Facility for assistance with FACS analysis. We also thank Adam Kohn and Mehrdad Jazayeri for helpful comments on the manuscript.
Funding AgencyGrant Number
Subject Keywords:AAV vectors, Optogenetics, primate, neutralizing antibodies
Issue or Number:5
PubMed Central ID:PMC5411474
Record Number:CaltechAUTHORS:20170222-102452242
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Official Citation:AAV-mediated delivery of optogenetic constructs to the macaque brain triggers humoral immune responses Skyler D. Mendoza, Yasmine El-Shamayleh, Gregory D. Horwitz Journal of Neurophysiology May 2017, 117 (5) 2004-2013; DOI: 10.1152/jn.00780.2016
Usage Policy:No commercial reproduction, distribution, display or performance rights in this work are provided.
ID Code:74465
Deposited By: Tony Diaz
Deposited On:22 Feb 2017 19:24
Last Modified:11 Nov 2021 05:27

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