At least nine different vaccines are currently in clinical trials for treating Alzheimer’s disease. While none of these vaccine candidates have started Phase 3 clinical trials, the data presented by drug companies at the 16th Annual Clinical Trials in Alzheimer’s Disease (CTAD) suggests they’re a promising avenue for exploring new treatments. 

In contrast to monoclonal antibodies, which are infused intravenously to clear specific plaques in the brain, vaccines teach the body’s immune system how to make its own antibodies against these targets. Scientists believe that these vaccines could give existing drugs like Leqembi a boost and may even prevent Alzheimer’s if administered earlier.

Teaching the immune system to fight amyloid in the brain

In the Phase 2 trial, Araclon Biotech’s vaccine ABVac40  — which targets one specific form of beta-amyloid called Aβ40 — was shown to be safe in a Phase 2 trial of 124 patients with mild cognitive impairment or very mild Alzheimer’s disease. The trial was done in a cohort of 124 patients over two years. Half of the participants received a vaccine regimen, while the other half received a placebo. 

Throughout the study, patients received a monthly vaccine for the first five months, followed by one booster shot half a year later. While the researchers found that the vaccines induced an immune response in the patients, they did not see a slowing in disease progression. Patients who received the vaccine did not have an increased chance of developing ARIA — brain swelling or microbleeds— a safety concern for anti-amyloid drugs like. A larger trial will be required to determine whether this vaccine is effective for patients.

Targeting tau to stop Alzheimer’s in its tracks

In contrast to ABvac40, Axon Neuroscience vaccine AADvac1 targets tau tangles in the brain, associated with Alzheimer’s disease progression. For their Phase 2 trial, Axon Neuroscience recruited 196 participants, randomized between a treatment and placebo group. The vaccine regimen consisted of six doses spaced out over four-week intervals, followed by boosters every 14 weeks. 

The participants who were positive for amyloid and tau biomarkers who received the vaccine showed cognitive improvement at the end of the two-year study. The next step is testing the vaccine in larger trials, and also seeing whether it can provide an immune boost to patients taking anti-amyloid drugs.

By the end of next year, there will be several new clinical trials of these vaccines. Research volunteers will help us understand more about the potential of this new class of preventions and treatments.