Name: AADvac1
Synonyms: Axon peptide 108 conjugated to KLH
Therapy Type: Immunotherapy (active) (timeline)
Target Type: Tau (timeline)
Condition(s): Alzheimer's Disease, Progressive Nonfluent Aphasia
U.S. FDA Status: Alzheimer's Disease (Phase 2), Progressive Nonfluent Aphasia (Phase 1)
Company: Axon Neuroscience SE


This is an active vaccine designed to elicit an immune response against pathologically modified forms of tau protein. The approach was inspired by research on tau cleavage generating N-terminally truncated fragments (Feb 2013 newsPaholikova et al., 2015). 

The AADvac1 vaccine consists of a synthetic peptide derived from amino acids 294 to 305 of the tau sequence, i.e., KDNIKHVPGGGS, coupled to keyhole limpet hemocyanin; the precise molecular nature of the antigen has not been disclosed. AADvac1 uses aluminum hydroxide as an adjuvant. At the 2014 AAIC conference in Copenhagen, preclinical studies were reported as having met safety requirements for up to six months in rats, rabbits, and dogs; a paper reported that the vaccine reduced tau pathology and improved sensorimotor function in transgenic rats (Aug 2014 newsKontsekova et al., 2014).


In May 2013, Axon Neuroscience began a first-in-man Phase 1 trial at four sites in Austria to evaluate AADvac1 in 30 patients with mild to moderate Alzheimer’s disease. Three subcutaneous, monthly injections of a single dose were assessed for safety, tolerability, and immunogenicity; some exploratory assessment of cognition was also done. A three-month, double-blind, placebo-controlled phase was followed by another three months of open-label monthly dosing. The treatment group received a total of six injections; placebo participants received three. After that, patients could enroll in a follow-up study lasting a further 18 months. By the end, 25 participants had received a total of six monthly injections plus one or two booster shots.

At the July 2015 AAIC conference, the company announced results. Twenty-four patients had been randomized to AADvac-1 and six to placebo, according to Reinhold Schmidt of the University of Graz. Two withdrew due to adverse events, of which one—a viral infection followed by epileptic seizure—was considered to be possibly related to the study medication. Overall, AADvac1 in this study was safe and well-tolerated, Schmidt said. In a majority of participants, repeat injections induced increasing antibody titers. Sera from immunized patients reacted with pathological tau from human brain. Mean ADAS-cog scores remained stable over six months. The results were later published (Novak et al., 2017).

In the 18-month open-label follow-up of 25 patients, antibody titers declined in the six months after last injection; booster doses restored IgG levels. The scientists saw no additional treatment-related serious adverse events, but reported a trend toward lower hippocampal atrophy and better performance on some cognitive tests in patients with higher IgG responses (Novak et al., 2018).  

In March 2016, a 24-month Phase 2 safety trial began enrolling 185 patients with mild to moderate AD and an MRI consistent with this diagnosis. Initially, the inclusion criteria included indications of medial temporal lobe atrophy; during the study the criteria were changed to medial temporal lobe atrophy and/or a positive AD biomarker profile of amyloid and tau in CSF. The study lists 30 exclusion criteria. It compares 11 subcutaneous injections of 40 micrograms of vaccine with the adjuvant aluminum hydroxide to placebo. The primary outcome is safety; secondary outcomes include cognitive and clinical batteries as well a measure of immunogenicity. FDG PET, MRI volumetry, and CSF biochemistry constitute exploratory outcomes. The study was conducted in Austria, the Czech Republic, Germany, Poland, Romania, Slovakia, Slovenia, and Sweden, and was slated to run until February 2019.

In September 2019, Axon Neuroscience announced topline results. According to a press release, the trial generated no differences in the incidence or type of adverse events between treatment and placebo groups. Of 196 patients studied, 98.2 percent generated antibodies against tau. AADvac-1 slowed the increase in blood levels of neurofilament light chain, a marker for neurodegeneration. In vaccinated patients, blood NfL rose 12.6 percent between baseline and two years versus a 27.87 percent rise in placebo-treated patients (p=0.0039). A smaller, unspecified number of patients who provided CSF reportedly saw trends in reduction of pTau181 and pTau217. The press release noted “positive signals” for the CDR-SB and other cognitive and imaging endpoints in younger people, but gave no details.

In July 2017, Axon Neuroscience started a two-year, open-label Phase 1 pilot trial of two doses of AADvac1 in 30 people with nonfluent/agrammatic variant primary progressive aphasia (PPA) between the ages of 18 and 85. Participants receive either 40 or 160 micrograms of AADvac1 in a series of six subcutaneous injections spaced six weeks apart, followed by five booster shots spaced 13 weeks apart. Primary outcomes include adverse events and measures of immunogenicity such as anti-AADvac1 antibody titer and subclass. Secondary outcomes include change in CSF biomarkers such as neurogranin, phosphorylated neurofilament heavy chain protein, ubiquitin, β-synuclein, tau, phospho-tau pT181, N-terminal tau, amyloid β1-40, amyloid-β1-42, ubiquitin, α-, β-, and γ-synuclein, YKL-40, MCP-1; change in serum biomarkers such as neurofilament light; MRI, as well as a range of clinical measures including the Frontotemporal Lobar Degeneration Clinical Dementia Rating Sum of Boxes (FTLD-CDR-SB) and others. The trial will run at three sites in Germany until July 2020.

For details on AADvac1 trials, see

Clinical Trial Timeline

  • Phase 1
  • Phase 2
  • Study completed / Planned end date
  • Planned end date unavailable
  • Study aborted
Sponsor Clinical Trial 2011 2012 2013 2014 2015 2016 2017 2018 2019 2020 2021 2022 2023 2024 2025 2026 2027 2028 2029 2030
Axon Neuroscience SE NCT01850238
Axon Neuroscience SE NCT02031198
Axon Neuroscience SE NCT02579252

Last Updated: 19 Sep 2019


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News Citations

  1. Truncated Tau Triggers Tangles, Transmits Pathology
  2. Therapies Take Aim at Tau

Paper Citations

  1. . Safety and immunogenicity of the tau vaccine AADvac1 in patients with Alzheimer's disease: a randomised, double-blind, placebo-controlled, phase 1 trial. Lancet Neurol. 2017 Feb;16(2):123-134. Epub 2016 Dec 10 PubMed.
  2. . FUNDAMANT: an interventional 72-week phase 1 follow-up study of AADvac1, an active immunotherapy against tau protein pathology in Alzheimer's disease. Alzheimers Res Ther. 2018 Oct 24;10(1):108. PubMed.
  3. . N-terminal truncation of microtubule associated protein tau dysregulates its cellular localization. J Alzheimers Dis. 2015;43(3):915-26. PubMed.
  4. . First-in-man tau vaccine targeting structural determinants essential for pathological tau-tau interaction reduces tau oligomerisation and neurofibrillary degeneration in an Alzheimer's disease model. Alzheimers Res Ther. 2014;6(4):44. Epub 2014 Aug 1 PubMed.

External Citations

  1. press release

Further Reading


  1. . Who fans the flames of Alzheimer's disease brains? Misfolded tau on the crossroad of neurodegenerative and inflammatory pathways. J Neuroinflammation. 2012;9:47. PubMed.
  2. . The self-perpetuating tau truncation circle. Biochem Soc Trans. 2012 Aug;40(4):681-6. PubMed.
  3. . Misfolded truncated protein τ induces innate immune response via MAPK pathway. J Immunol. 2011 Sep 1;187(5):2732-9. PubMed.
  4. . Tau truncation is a productive posttranslational modification of neurofibrillary degeneration in Alzheimer's disease. Curr Alzheimer Res. 2010 Dec;7(8):708-16. PubMed.