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Protective anti‐prion antibodies in human immunoglobulin repertoires

Senatore, Assunta and Frontzek, Karl and Emmenegger, Marc and Chincisan, Andra and Losa, Marco and Reimann, Regina and Horny, Geraldine and Guo, Jingjing and Fels, Sylvie and Sorce, Silvia and Zhu, Caihong and George, Nathalie and Ewert, Stefan and Pietzonka, Thomas and Hornemann, Simone and Aguzzi, Adriano (2020) Protective anti‐prion antibodies in human immunoglobulin repertoires. EMBO Molecular Medicine, 12 (9). pp. 1-19. ISSN 1757-46761757-4684

Abstract

Prion immunotherapy may hold great potential, but antibodies against certain PrP epitopes can be neurotoxic. Here, we identified > 6,000 PrP‐binding antibodies in a synthetic human Fab phage display library, 49 of which we characterized in detail. Antibodies directed against the flexible tail of PrP conferred neuroprotection against infectious prions. We then mined published repertoires of circulating B cells from healthy humans and found antibodies similar to the protective phage‐derived antibodies. When expressed recombinantly, these antibodies exhibited anti‐PrP reactivity. Furthermore, we surveyed 48,718 samples from 37,894 hospital patients for the presence of anti‐PrP IgGs and found 21 high‐titer individuals. The clinical files of these individuals did not reveal any enrichment of specific pathologies, suggesting that anti‐PrP autoimmunity is innocuous. The existence of anti‐prion antibodies in unbiased human immunological repertoires suggests that they might clear nascent prions early in life. Combined with the reported lack of such antibodies in carriers of disease‐associated PRNP mutations, this suggests a link to the low incidence of spontaneous prion diseases in human populations.

Item Type: Article
Date Deposited: 26 Sep 2020 00:45
Last Modified: 26 Sep 2020 00:45
URI: https://oak.novartis.com/id/eprint/42126

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