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An Amyloid beta (Abeta) vaccine that safely drives immunity to a key pathological species in Alzheimer’s disease: pyroglutamate Abeta

M. Vukicevic, E. Fiorini, S. Siegert, R. Carpintero, M. Rincon, P. Lopez-Deber, N. Piot, M. Ayer, I. Rentero, C. Babolin, S. Bravo-Veyrat, V. Giriens, C. Morici, M. Beuzelin, A. Gesbert, S. Rivot, S. Depretti, P. Donati, J. Streffer, A. Pfeifer, M. H. Kosco-Vilbois

Preclinical results of our wholly owned anti-Abeta vaccine program ACI-24 show that the optimized formulation generates a potent and sustained immune response. Antibodies showed binding to pyroglutamate Abeta, a highly neurotoxic form of Abeta, which, following recent proof-of-concept from a monoclonal antibody, is a promising target for Alzheimer therapy.

Brain Communications, https://doi.org/10.1093/braincomms/fcac022

Published: 04 February 2022

AC Immune's scientific publications

09/05/2022 Rafii M et al., JAMA Neurology, 2022

Safety, Tolerability, and Immunogenicity of the ACI-24 Vaccine in Adults With Down Syndrome: A Phase 1b Randomized Clinical Trial

Rafii MS, Sol O, Mobley WC, Delpretti S, Skotko BG, Burke AD, Sabbagh MN, Yuan SH, Rissman RA, Pulsifer M, Evans C, Carol Evans A, Beth G, Fournier N, Gray JA, Melo dos Santos A, Hliva V, Vukicevic M, Kosco-Vilbois M, Streffer J, Pfeifer A, Feldman HH
04/02/2022 Vukicevic M et al., Brain Communications, 2022

An Amyloid beta (Abeta) vaccine that safely drives immunity to a key pathological species in Alzheimer’s disease: pyroglutamate Abeta

Vukicevic M, Fiorini E, Siegert S, Carpintero R, Rincon M, Lopez-Deber P, Piot N,  Ayer M, Rentero I, Babolin C, Bravo-Veyrat S, Giriens V, Morici C, Beuzelin M, Gesbert A, Rivot S, Depretti S, Donati P, Streffer J, Pfeifer A, Kosco-Vilbois MH
15/12/2021 Kroth H et al., Bioorg. Med. Chem., 2021

Structure-activity relationship around PI-2620 highlights the importance of the nitrogen atom position in the tricyclic core

Kroth H, Oden F, Serra AM, Molette J, Mueller A, Berndt M, Capotosti F, Gabellieri E, Schmitt-Willich H, Hickman D, Pfeifer A, Dinkelberg L, Stephens A
29/08/2021 Kroth H et al., J. Med. Chem. 2021

PI-2620 lead optimization highlights the importance of off-target assays to develop a pet tracer for the detection of pathological aggregated tau in Alzheimer’s disease and other tauopathies

Kroth H, Oden F, Molette J, Schieferstein H, Gabellieri E, Mueller A, Berndt M, Sreenivasachary N, Serra AM, Capotosti F, Schmitt-Willich H, Hickman D, Pfeifer A, Dinkelborg L, and Stephens A
12/05/2021 Ayalon G et al., Sci. Transl. Med., 2021

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Ayalon G, Lee S-H, Adolfsson O, Foo-Atkins C, Atwal JK, Blendstrup M,  Booler H, Bravo J, Brendza R, Brunstein F, Chan R, Chandra P, Couch JA, Datwani A, Demeule B, DiCara D, Erickson R, Ernst JA, Foreman O, He D, Hötzel I, Keeley M, Kwok MCM, Lafrance-Vanasse J, Lin H, Lu Y,  Luk W, Manser P, Muhs A, Ngu H, Pfeifer A, Pihlgren M, Rao GK, Scearce-Levie K, Schauer SP, Smith WB, Solanoy H, Teng E, Wildsmith KR, Bumbaca Yadav  D, Ying Y, Fuji RN, Kerchner GA
15/10/2020 Gabellieri E et al. , Eur. J. Med. Chem., 2020

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Gabellieri E, Capotosti F, Molette J, Sreenivasachary N, Mueller A, Berndt M, Schieferstein H, Juergens T, Varisco Y, Oden F, Schmitt-Willich H, Hickman D, Dinkelborg L, Stephens A, Pfeifer A, Kroth H
11/11/2019 Bullich S et al., J. Nucl. Med., 2019

Evaluation of dosimetry, quantitative methods and test-retest variability of 18F-PI-2620 PET for the assessment of Tau deposits in the human brain

Bullich S, Barret O, Constantinescu C, Sandiego C, Mueller A, Papin C, Perrotin A, Koglin N, Kroth H, Pfeifer A, Madonia J, Seiby JP, Marek K, de Santi, Dinkelborg LM, Berndt M, Tamagnan G, Stephens AW
11/11/2019 Mueller A et al., J. Nucl. Med., 2019

Tau PET imaging with 18F-PI-2620 in patients with Alzheimer's disease and healthy controls: a first-in-human study

Mueller A, Bullich S, Barret O, Madonia J, Berndt M, Papin C, Perrotin A, Koglin N, Kroth H, Pfeifer A, Tamagnan G, Seibyl JP, Marek K, de Santi S, Dinkelborg LM, Stephens AW
20/09/2019 Sreenivasachary N et al., Org. Process Res. Dev., 2019

A Short Synthesis of the 2-Bromo-N,9-dimethyl-6,7,8,9-tetrahydro-5H-pyrido[2,3-b]indol-6-amine Building Block

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01/07/2019 Kroth H et al., Eur. J. Nucl. Med. Mol. Imaging , 2019

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Kroth H, Oden F, Molette J, Schieferstein H, Capotosti F, Mueller A, Berndt M, Schmitt-Willich H, Darmency V, Gabellieri E, Boudou C, Juergens T, Varisco Y, Vokali E, Hickman DT, Tamagnan G, Pfeifer A, Dinkelborg L, Muhs A, Stephens AW
13/11/2018 Chen H-H et al., Scientific Reports, 2018

Calpain-mediated tau fragmentation is altered in Alzheimer’s disease progression

Hsu-Hsin Chen, Peter Liu, Paul Auger, Seung-Hye Lee, Oskar Adolfsson, Lorianne Rey-Bellet, Julien Lafrance-Vanasse, Brad A. Friedman, Maria Pihlgren, Andreas Muhs, Andrea Pfeifer, James Ernst, Gai Ayalon, Kristin R. Wildsmith, Thomas G. Beach & Marcel P. van der Brug
19/10/2017 Lathuilière A et al., Scientific Reports, 2017

Motifs in the tau protein that control binding to microtubules and aggregation determine pathological effects

Aurélien Lathuilière, Pamela Valdés, Stéphanie Papin, Matthias Cacquevel, Catherine Maclachlan, Graham W. Knott, Andreas Muhs, Paolo Paganetti, Bernard L. Schneider
15/03/2017 Sreenivasachary N et al., Bioorganic & Medicinal Chemistry Letters, 2017

Discovery and characterization of novel indole and 7-azaindole derivatives as inhibitors of β-amyloid-42 aggregation for the treatment of Alzheimer’s disease

Nampally Sreenivasachary, Heiko Kroth, Pascal Benderitter, Anne Hamel, Yvan Varisco, David T. Hickman, Wolfgang Froestl, Andrea Pfeifer, Andreas Muhs
20/12/2016 Ultsch M et al., Scientific Reports, 2016

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Mark Ultsch, Bing Li, Till Maurer, Mary Mathieu, Oskar Adolfsson, Andreas Muhs, Andrea Pfeifer, Maria Pihlgren, Travis W. Bainbridge, Mike Reichelt, James A. Ernst, Charles Eigenbrot, Germaine Fuh, Jasvinder K. Atwal, Ryan J. Watts, Weiru Wang
02/11/2016 Theunis C et al., J. Alzheimer. Dis., 2016

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09/08/2016 Lee S-H et al., Cell Reports, 2016

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15/07/2016 Kroth H et al., Bioorganic & Medicinal Chemistry Letters, 2016

Synthesis and structure–activity relationship of 2,6-disubstituted pyridine derivatives as inhibitors of b-amyloid-42 aggregation

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Dynamic nuclear polarization NMR spectroscopy: revealing multiple conformations in lipid-anchored peptide vaccines

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19/08/2013 Theunis C et al., PLoS One, 2013

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Theunis C, Crespo-Biel N, Gafner V, Pihlgren M, Lopez-Deber P, Reis P, Hickman D, Adolfsson O, Chuard N, Mlaki Ndao D, Borghgraef P, Devijver H, Van Leuven F, Pfeifer A, Muhs A
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An optimized Amyloid beta vaccine that safely drives immunity to the key pathological species of Alzheimer's disease

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