AC Immune

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,

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
12/05/2021 Ayalon G et al., Sci. Transl. Med., 2021

Antibody semorinemab reduces tau pathology in a transgenic mouse model and engages tau in patients with Alzheimer's disease

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

Discovery of 2-(4-(2-fluoroethoxy)piperidin-1-yl)-9-methyl-9H-pyrrolo[2,3-b:4,5-c']dipyridine ([18F]PI-2014) as PET tracer for the detection of pathological aggregated Tau in Alzheimer's disease and other tauopathies

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

Sreenivasachary N, Kroth H, Benderitter P, Barth W, Pfeifer A, Muhs A
01/07/2019 Kroth H et al., Eur. J. Nucl. Med. Mol. Imaging , 2019

Discovery and preclinical characterization of [18F]PI-2620, a next-generation tau PET tracer for the assessment of tau pathology in Alzheimer’s disease and other tauopathies

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

Structure of Crenezumab Complex with Aβ Shows Loss of β-Hairpin

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

Novel Phospho-Tau Monoclonal Antibody Generated Using a Liposomal Vaccine, with Enhanced Recognition of a Conformational Tauopathy Epitope

Clara Theunis, Oskar Adolfsson, Natalia Crespo-Biel, Kasia Piorkowska, Maria Pihlgren, David T. Hickman, Valerie Gafner, Peter Borghgraef, Herman Devijver, Andrea Pfeifer, Fred Van Leuven, Andreas Muhs
09/08/2016 Lee S-H et al., Cell Reports, 2016

Antibody-mediated targeting of Tau in vivo does not require effector function and microglial engagement

Seung-Hye Lee, Claire E. Le Pichon, Oskar Adolfsson, Valerie Gafner, Maria Pihlgren, Han Lin,Hilda Solanoy, Robert Brendza, Hai Ngu, Oded Foreman, Ruby Chan,James A. Ernst, Danielle DiCara, Isidro Hotzel, Karpagam Srinivasan, David V. Hansen, Jasvinder Atwal, Yanmei Lu, Daniela Bumbaca, Andrea Pfeifer, Ryan J. Watts, Andreas Muhs, Kimberly Scearce-Levie and Gai Ayalon
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

Heiko Kroth, Nampally Sreenivasachary, Anne Hamel, Pascal Benderitter, Yvan Varisco, Valérie Giriens, Paolo Paganetti, Wolfgang Froestl, Andrea Pfeifer, Andreas Muhs
29/03/2016 Belichenko PV et al., PLOS one, 2016

An Anti-Beta-Amyloid Vaccine for Treating Cognitive Deficits in a Mouse Model of Down Syndrome

Pavel V. Belichenko, Rime Madani, Lorianne Rey-Bellet, Maria Pihlgren, Ann Becker, Adeline Plassard, Stephanie Vuillermot, Valérie Giriens, Rachel L. Nosheny, Alexander M. Kleschevnikov, Janice S. Valletta, Sara K. S. Bengtsson, Gordon R. Linke, Michael T. Maloney, David T. Hickman, Pedro Reis, Anne Granet, Dorin Mlaki, Maria Pilar Lopez-Deber, Long Do, Nishant Singhal, Eliezer Masliah, Matthew L. Pearn, Andrea Pfeifer, Andreas Muhs, William C. Mobley
13/10/2015 Devraj K et al., JCBFM, 2015

BACE-1 is expressed in the blood - brain barrier endothelium and is upregulated in a murine model of Alzheimer's disease

Kavi Devraj, Slobodan Poznanovic, Christoph Spahn, Gerhard Schwall, Patrick N Harter, Michel Mittelbronn, Katia Antoniello, Paolo Paganetti, Andreas Muhs, Mike Heilemann, Richard A Hawkins, André Schrattenholz, Stefan Liebner
05/11/2014 Mlaki Ndao D et al., BioProtocol, 2014

Binding Affinity Measurement of Antibodies from Crude Hybridoma Samples by SPR

Dorin Mlaki Ndao, David T. Hickman, María Pilar López-Deber, Aurélien Davranche, Andrea Pfeifer, Andreas Muhs
10/09/2014 Lopez Deber MP et al., PLoS One, 2014

Engineering Amyloid-Like Assemblies from Unstructured Peptides via Site-Specific Lipid Conjugation

Maria Pilar Lopez Deber, David T. Hickman, Deepak Nand , Marc Baldus, Andrea Pfeifer, Andreas Muhs
25/07/2014 Froestl W et al., Journal of Alzheimer's disease, 2014

Cognitive enhancers (Nootropics). Part 1: drugs interacting with receptors

Froestl W, Muhs A, Pfeifer A
25/03/2014 Froestl W et al., Journal of Alzheimer's disease, 2014

Cognitive enhancers (nootropics). Part 2: drugs interacting with enzymes

Froestl W, Muhs A, Pfeifer A
21/10/2013 Papassotiropoulos A et al., PNAS, 2013

Human genome-guided identification of memory-modulating drugs

Papassotiropoulos A, Gerhards C, Heck A, Ackermann S, Aerni A, Schicktanz N, Auschra B, Demougin P, Mumme E, Elbert T, Ertl V, Gschwind L, Hanser E, Huynh KD, Jessen F, Kolassa IT, Milnik A, Paganetti P, Spalek K, Vogler C, Muhs A, Pfeifer A, de Quervain DJ
23/08/2013 Koers E et al., Angewandte Chemie International Edition, 2013

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

Koers E, López-Deber MP, Weingarth M, Nand D, Hickman DT, Mlaki Ndao D, Reis P, Granet A, Pfeifer A, Muhs A, Baldus M
19/08/2013 Theunis C et al., PLoS One, 2013

Efficacy and Safety of A Liposome-Based Vaccine against Protein Tau, Assessed in Tau.P301L Mice That Model Tauopathy

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
06/08/2013 Paganetti P et al., J. Alzheimers Dis., 2014

Increased efflux of amyloid-β peptides through the blood-brain barrier by muscarinic acetylcholine receptor inhibition reduces pathological phenotypes in mouse models of brain amyloidosis

Paganetti P, Antoniello K, Devraj K, Toni N, Kieran D, Madani R, Pihlgren M, Adolfsson O, Froestl W, Schrattenholz A, Liebner S, Havas D, Windisch M, Cirrito JR, Pfeifer A, Muhs A
06/02/2013 Froestl W et al., Journal of Alzheimer's disease, 2013

Cognitive enhancers (Nootropics). Part 3: drugs interacting with targets other than receptors or enzymes. Disease-modifying drugs.

Froestl W, Muhs A, Pfeifer A
03/01/2013 Pihlgren M et al., Blood, 2013

TLR4 and TRIF-dependent stimulation of B lymphocytes by peptide liposomes enables T-cell independent isotype switch in mice

Pihlgren M, Silva AB, Madani R, Giriens V, Waeckerle-Men Y, Fettelschloss A, Hickman D, Lopez-Deper MP, Mlaki Ndao D, Vukicevic M, Bucarello AL, Gafner V, Chuard N, Reis P, Piorkowska K, Pfeifer A, Kündig TM, Muhs A, Johansen P
18/03/2022 Smith R et al., AD/PDTM 2022

Initial scans using [18F]ACI-12589, a novel PET-tracer for a-synuclein

Ruben Smith, Francesca Capotosti, Martin Schain , Tomas Ohlsson, Efthymia Vokali , Tanja Touilloux, Valérie Hliva, Jérôme Molette, Yannis Dimitrakopoulos, Erik Stomrud , Sara Hall, Klas Bratteby , Elina Tampio L’Estrade , Ruth Luthi-Carter, Andrea Pfeifer, Marie Kosco-Vilbois, Johannes Streffer, Oskar Hansson
15/03/2022 Capotosti F et al., AD/PDTM 2022

Discovery of [18F]ACI-12589, a novel and promising PET-tracer for a-synuclein

Francesca Capotosti, Efthymia Vokali, Jérôme Molette, Myriam Ravache1, Christophe Delgado, Jacqueline Kocher, Laure Pittet, Kasia Piorkowska, Ruth Luthi-Carter, Tanja Touilloux, Valérie Hliva, Ruben Smith, Oskar Hansson, Johannes Streffer, Andrea Pfeifer, Marie Kosco-Vilbois
15/03/2022 Vukicevic M et al., AD/PDTM 2022

An optimized Amyloid beta vaccine that safely drives immunity to the key pathological species of Alzheimer's disease

M. Vukicevic, E. Fiorini, R. Carpintero, M. Rincon, P. Lopez-Deber, N. Piot, M. Ayer, I. Rentero, S. Siegert, C. Babolin, D. Knittel, E. Gollwitzer, S. Bravo-Veyrat, V. Giriens, C. Morici, M. Beuzelin, A. Gesbert, S. Rivot, N. Chuard, V. Attanasio, S. Delpretti, P. Donati, J. Streffer, A. Pfeifer and M. Kosco-Vilbois
15/03/2022 Seredenina T et al., AD/PDTM 2022

Optimization of PET tracers for TDP-43 proteinopathies

Tamara Seredenina, Tariq Afroz, Nicolas Dreyfus, Simone Hargraves, Jacqueline Kocher, Lorene Mottier, Mayank Chauhan, Elodie Chevallier, Vincent Darmency, Heiko Kroth, Andrea Pfeifer, Marie Kosco-Vilbois
15/03/2022 Afroz T et al., AD/PDTM 2022

TDP-43 immunotherapy decreases neuropathology and confers neuroprotection through microglial engagement in mouse models of ALS/FTD

Tariq Afroz, Tamara Seredenina, Elodie Chevalier, Tamar Ziehm, Mickael Audrain, Anne-Laure Egesipe, Lorène Mottier, Manuela Neumann, Romain Ollier, Kasia Piorkowska, Mayank Chauhan, Christopher Dumayne, Samjhana Thapa, Jan Stöhr, Valerie Eligert, Oskar Adolfsson, Sílvia Porta, Virginia M.-Y. Lee, Andrea Pfeifer, Marie Kosco-Vilbois
09/11/2021 Streffer J et al., CTAD, 2021

ACI-35.030, a novel anti-phosphoTau vaccine for the treatment of Alzheimer’s Disease: Interim data on safety, tolerability and immunogenicity

Johannes Streffer, Bénédicte Lê, Olivier Sol, Marija Vukicevic, Emma Fiorini, Eva Gollwitzer, Valérie Hliva, Julien Mermoud, David Hickman, Julian Gray, Antonio Melo dos Santos, Nicolas Piot, Julien Rongère, Andrea Pfeifer, Marie Kosco-Vilbois, Philip Scheltens