Background

This active vaccine was designed to overcome the weak immune system of aged populations while avoiding auto-immune T cell responses. The Lu AF20513 epitope intersperses three repeats of the first 12 amino acids of the Aβ peptide with sequences of tetanus toxin. The goal of this kind of mixed-peptide engineering is to rouse an elderly population of non-self memory T cells originally generated by childhood tetanus vaccinations to stimulate T helper cells, which in turn activate a B cell response to produce polyclonal antibodies against Aβ. A preclinical study in mice, guinea pigs, and monkeys characterized the cellular and humoral immune response against this vaccine, reporting high Aβ titers, no autoreactive T cells, and removal of brain amyloid deposits (Davtyan et al., 2013). 

Findings

In March 2015, an open-label Phase 1 trial started to enroll 50 people with probable Alzheimer's disease, a CSF Aβ antibody measurement, and a recent MRI consistent with an AD diagnosis. The trial administered multiple shots of either a low, medium, high, or double-high dose to participants, and measured antibody titers as well as safety and tolerability over a period of two years. It took place in Austria, Finland, and Sweden. The trial was terminated in November 2019.

For more detail, see clinicaltrials.gov.