Aadvac1 Tau Vaccine is an important component in the neurobiology of neurodegenerative diseases. This page provides detailed information about its structure, function, and role in disease processes.
AADvac1 is an active immunotherapy vaccine targeting pathological tau protein, developed by Axon Neuroscience SE for the treatment of Alzheimer's disease and other tauopathies. It represents a novel disease-modifying approach aimed at clearing or preventing the formation of neurofibrillary tangles. [1]
| Property | Value | [2]
|----------|-------| [3]
| Category | Treatments | [4]
| Target | Pathological tau protein | [5]
| Approach | Active immunotherapy (vaccine) | [6]
| Status | Phase II (ADAMANT AD trial completed; PSP platform trial enrolled) | [7]
| Developer | Axon Neuroscience SE |
AADvac1 is a synthetic peptide vaccine designed to elicit antibodies against specific epitopes of pathological tau protein:
Upon administration, AADvac1 stimulates the immune system to produce antibodies that:
The vaccine targets multiple forms of pathological tau:
AADvac1 is now being evaluated in the PSP Clinical Trial Platform (NCT07173803), a multi-center adaptive platform trial led by University of Pennsylvania. This represents the first evaluation of AADvac1 specifically in PSP patients.
AADvac1 targets pathological tau, which is the hallmark protein aggregation in PSP (a 4R-tauopathy). The vaccine generates antibodies against phosphorylated tau epitopes (pSer396, pSer404) that can help clear toxic tau species and potentially slow disease progression.
The platform design allows multiple treatments to be evaluated under a single protocol, with shared control groups, making it efficient for rare diseases like PSP.
A 2024 post-hoc analysis of the ADAMANT trial focused on 137 participants who were positive for plasma p-tau217 at baseline[@kovacech2024]. This analysis revealed:
This analysis supports the hypothesis that AADvac1 may be most effective in patients with confirmed tau pathology, and that antibody titer is an important predictor of treatment response.
AADvac1 has been selected as a treatment arm in the Progressive Supranuclear Palsy (PSP) Clinical Trial Platform (NCT07173803), a multi-center, multi-regimen adaptive platform trial sponsored by the University of Pennsylvania[8].
PSP is pathologically characterized by accumulation of 4-repeat tau in neurofibrillary tangles and glial lesions. AADvac1 targets multiple tau isoforms, making it potentially relevant for PSP as well as Alzheimer's disease. The vaccine aims to:
The platform is designed with approximately 5-year milestones:
The platform also includes LM11A-31 (Astellas Pharma), a small molecule p75NTR modulator that targets neuronal survival pathways. This allows for potential combination insights as the trial progresses.
| Vaccine | Type | Status | Key Features |
|---|---|---|---|
| AADvac1 | Active | Phase II | Tau pSer396/404 |
| ACI-35 | Active | Phase I | Phospho-tau liposomal |
| BMS-986036 | Passive | Phase II | Anti-tau antibody |
AADvac1 is now being evaluated in a PSP Clinical Trial Platform (also known as a platform trial), which represents an innovative approach to testing multiple therapeutic candidates in parallel for Progressive Supranuclear Palsy. This adaptive platform trial employs response-adaptive randomization and Bayesian statistical methods to efficiently identify effective treatments.
Platform Trial Details:
Relevance to PSP: PSP is pathologically characterized by accumulation of 4-repeat tau in neurofibrillary tangles and glial lesions. AADvac1 targets multiple tau isoforms, including the 4-repeat tau predominant in PSP, making it potentially relevant for PSP as well as Alzheimer's disease. The vaccine's mechanism of stimulating antibodies against pathological tau may help clear tau aggregates that drive neurodegeneration in PSP.
Status: Enrollment ongoing; interim analysis results pending. The platform design allows for efficient evaluation of multiple candidates and potential regulatory pathways based on platform-level data.
Axon Neuroscience SE is a Slovakian biotechnology company headquartered in Bratislava, founded in 1999 as a spin-off from the Institute of Neuroimmunology of the Slovak Academy of Sciences. The company has focused exclusively on tau-targeted therapeutics for neurodegenerative diseases, making it one of the few companies with a dedicated tau franchise.
The company was founded by Professor Michal Novak, a renowned neuroscientist who has dedicated over three decades to tau research. Professor Novak's pioneering work on tau protein structure and pathology has been instrumental in shaping the development of AADvac1. The scientific advisory board includes leading tau researchers from academic institutions across Europe and the United States.
Axon Neuroscience has developed a proprietary vaccine platform that combines:
Beyond AADvac1, Axon Neuroscience has developed additional tau-targeting candidates:
The selection of phosphorylated serine residues 396 and 404 as target epitopes was based on several key considerations:
Detailed epitope mapping studies have shown that AADvac1-induced antibodies recognize:
This broad reactivity profile allows the vaccine to target multiple pathological tau conformations.
| Feature | ACI-35 | AADvac1 |
|---|---|---|
| Platform | Liposomal | KLH-conjugated peptide |
| Epitope | pSer396 | pSer396/404 |
| IgG Subclass | IgG1 | IgG1 (likely) |
| Status | Phase Ib/IIa | Phase II |
| Company | AC Immune | Axon Neuroscience |
The ADAMANT Phase 2 trial was a randomized, double-blind, placebo-controlled study conducted across 57 sites in 9 European countries.
Key Design Elements:
Statistical Considerations:
The NCT07173803 platform trial employs an innovative adaptive design:
Key Features:
AADvac1-Specific Endpoints:
Novak P, et al. (2021). ADAMANT: a placebo-controlled randomized phase 2 study of AADvac1 in Alzheimer's disease. Alzheimer's Research & Therapy. 2021. ↩︎
Kontsekova E, et al. (2014). First-in-man tau vaccine: structural rationale and results from first-in-human trial. CNS Drugs. 2014. ↩︎
Zilkova M, et al. (2020). Tau targeting vaccines for Alzheimer's disease and related tauopathies. Journal of Immunology Research. 2020. ↩︎
Sigurdsson EM. (2016). Tau immunotherapy. Neurodegenerative Diseases. 2016. ↩︎
Boutajangout A, et al. (2010). Vaccination as a therapeutic approach to Alzheimer's disease: Mounting evidence. Neurochemical Research. 2010. ↩︎
Cohen M, et al. (2021). Anti-tau antibody administration reduces tau pathology and improves cognition in mouse models. Journal of Experimental Medicine. 2021. ↩︎
Chernyak S, et al. (2021). Clinical development of anti-tau antibodies in Alzheimer's disease: current status and future prospects. Neurology and Therapy. 2021. ↩︎
The Progressive Supranuclear Palsy Clinical Trial Platform (NCT07173803). 2024. ↩︎