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
Notes: Article -- Export Date: 1 March 2019 -- Source: Scopus
Citation Impact
MSK Authors
  1. Yevgeniy Romin
    15 Romin