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Amyloid-β targeting immunisation in aged non-human primate (Microcebus murinus)

Stéphanie G. Trouche, Allal Boutajangout, Ayodeji Asuni, Pascaline Fontés, Einar M. Sigurdsson, Jean-Michel Verdier, Nadine Mestre-Francés
doi: https://doi.org/10.1101/2022.08.05.502918
Stéphanie G. Trouche
1MMDN Univ. Montpellier, EPHE, INSERM, Montpellier France
2PSL Research University, Paris, France
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Allal Boutajangout
3Departments of Neurology, and Neuroscience and Physiology, New York University Grossman School of Medicine, New York, United States
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Ayodeji Asuni
4Department of Psychiatry, New York University Grossman School of Medicine, New York, United States
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Pascaline Fontés
1MMDN Univ. Montpellier, EPHE, INSERM, Montpellier France
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Einar M. Sigurdsson
5Departments of Neuroscience and Physiology, and Psychiatry, Neuroscience Institute, New York University Grossman School of Medicine, New York, United States
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Jean-Michel Verdier
1MMDN Univ. Montpellier, EPHE, INSERM, Montpellier France
2PSL Research University, Paris, France
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Nadine Mestre-Francés
1MMDN Univ. Montpellier, EPHE, INSERM, Montpellier France
2PSL Research University, Paris, France
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  • For correspondence: nadine.frances@umontpellier.fr
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Abstract

Non-human primates have an important translational value given their close phylogenetic relationship to humans. Studies in these animals remain essential for evaluating efficacy and safety of new therapeutic approaches, particularly in aging primates that display Alzheimer’s disease (AD) -like pathology. With the objective to improve amyloid-β (Aβ) targeting immunotherapy, we investigated the safety and efficacy of an active immunisation with an Aβ derivative, K6Aβ1−30-NH2, in old non-human primates. Thirty-two aged (4-10 year-old) mouse lemurs were enrolled in the study, and received up to four subcutaneous injections of the vaccine in alum adjuvant or adjuvant alone.

Even though antibody titres to Aβ were not high, pathological examination of the mouse lemur brains showed significant reduction in intracellular Aβ without inflammatory or haemorrhagic changes. Moreover, a trend for cognitive improvement was observed in the vaccinated primates, which was probably linked to Aβ clearance. This Aβ derivative vaccine appeared to be safe as a prophylactic measure based on the brain analyses and because it did not appear to have detrimental effects on the general health of these old animals.

Competing Interest Statement

EM Sigurdsson is an inventor on patents and patent applications on Aβ immunotherapies that are assigned to New York University

Copyright 
The copyright holder for this preprint is the author/funder, who has granted bioRxiv a license to display the preprint in perpetuity. It is made available under a CC-BY-NC-ND 4.0 International license.
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Posted August 06, 2022.
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Amyloid-β targeting immunisation in aged non-human primate (Microcebus murinus)
Stéphanie G. Trouche, Allal Boutajangout, Ayodeji Asuni, Pascaline Fontés, Einar M. Sigurdsson, Jean-Michel Verdier, Nadine Mestre-Francés
bioRxiv 2022.08.05.502918; doi: https://doi.org/10.1101/2022.08.05.502918
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Amyloid-β targeting immunisation in aged non-human primate (Microcebus murinus)
Stéphanie G. Trouche, Allal Boutajangout, Ayodeji Asuni, Pascaline Fontés, Einar M. Sigurdsson, Jean-Michel Verdier, Nadine Mestre-Francés
bioRxiv 2022.08.05.502918; doi: https://doi.org/10.1101/2022.08.05.502918

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