Conformation-specific antibodies against multiple amyloid protofibril species from a single amyloid immunogen Journal Article
| Authors: | Bonito-Oliva, A.; Schedin-Weiss, S.; Younesi, S. S.; Tiiman, A.; Adura, C.; Paknejad, N.; Brendel, M.; Romin, Y.; Parchem, R. J.; Graff, C.; Vukojević, V.; Tjernberg, L. O.; Terenius, L.; Winblad, B.; Sakmar, T. P.; Graham, W. V. |
| Article Title: | Conformation-specific antibodies against multiple amyloid protofibril species from a single amyloid immunogen |
| Abstract: | We engineered and employed a chaperone-like amyloid-binding protein Nucleobindin 1 (NUCB1) to stabilize human islet amyloid polypeptide (hIAPP) protofibrils for use as immunogen in mice. We obtained multiple monoclonal antibody (mAb) clones that were reactive against hIAPP protofibrils. A secondary screen was carried out to identify clones that cross-reacted with amyloid beta-peptide (Aβ42) protofibrils, but not with Aβ40 monomers. These mAbs were further characterized in several in vitro assays, in immunohistological studies of a mouse model of Alzheimer's disease (AD) and in AD patient brain tissue. We show that mAbs obtained by immunizing mice with the NUCB1-hIAPP complex cross-react with Aβ42, specifically targeting protofibrils and inhibiting their further aggregation. In line with conformation-specific binding, the mAbs appear to react with an intracellular antigen in diseased tissue, but not with amyloid plaques. We hypothesize that the mAbs we describe here recognize a secondary or quaternary structural epitope that is common to multiple amyloid protofibrils. In summary, we report a method to create mAbs that are conformation-sensitive and sequence-independent and can target more than one type of protofibril species. © 2019 The Authors. Journal of Cellular and Molecular Medicine published by John Wiley & Sons Ltd and Foundation for Cellular and Molecular Medicine. |
| Keywords: | monoclonal antibody; amyloid; amyloid aggregation; alzheimer’s disease; chaperone-like amyloid-binding protein; conformation-sensitive; protofibril |
| Journal Title: | Journal of Cellular and Molecular Medicine |
| Volume: | 23 |
| Issue: | 3 |
| ISSN: | 1582-1838 |
| Publisher: | Wiley-Blackwell Publishing Ltd. |
| Date Published: | 2019-03-01 |
| Start Page: | 2103 |
| End Page: | 2114 |
| Language: | English |
| DOI: | 10.1111/jcmm.14119 |
| PUBMED: | 30663210 |
| PROVIDER: | scopus |
| PMCID: | PMC6378190 |
| DOI/URL: | |
| Notes: | Article -- Export Date: 1 March 2019 -- Source: Scopus |
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