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Alzheimer’s Vaccine Shown to Produce Immune Response

Brain activity graphic

(Gordon Johnson, Pixabay)

4 Feb. 2022. In tests with lab animals, an experimental vaccine is shown to generate antibodies responding to toxic brain proteins associated with Alzheimer’s disease. Findings from the study appear in Wednesday’s issue of the journal Brain Communications, assessing the vaccine code-named ACI-24 by its developer AC Immune SA in Lausanne, Switzerland.

AC Immune creates diagnostics, vaccines, and treatments for Alzheimer’s disease and other neurodegenerative disorders. Alzheimer’s disease is a progressive neurodegenerative condition, the most common form of dementia affecting growing numbers of older people worldwide. People with Alzheimer’s disease often have deposits of abnormal substances in spaces between brain cells, known as amyloid-beta proteins, as well as misfolded tangles of proteins inside brain cells known as tau. Data from Alzheimer’s Disease International show in 2020 more than 55 million people worldwide with dementia, at least half of those with Alzheimer’s disease, a number expected to grow to 139 million by 2050.

AC Immune uses two separate technologies to address toxic protein deposits, both amyloid-beta proteins that accumulate as plaques outside of neurons and tau that builds up inside neurons in the brain and spreads between cells. One of those technologies, called SupraAntigen, is the basis for treatments that generate antibodies in the immune system for attacking and breaking up toxic protein deposits, particularly before they cause irreversible damage to neurons.

High concentrations of antibodies

In this study, researchers from AC Immune tested ACI-24, a vaccine for preventing Alzheimer’s disease and treating the disorder in its early stages, in lab mice and monkeys. ACI-24, says the company, is produced with SupraAntigen as a synthetic peptide, or short chain of amino acids, with an adjuvant to enhance immune response, and carried in a lipid or natural oil container. In this case, the peptide in ACI-24 is designed to invoke an immune reaction, with antibodies to clear a toxic amyloid-beta protein known as pyroglutamate abeta3-42 or pGlu-Abeta3-42. And those generated antibodies specifically target 15 amino acids making up a key part of pGlu-Abeta3-42.

The study team says test animals well-tolerate ACI-24. Recipients of ACI-24, mice and monkeys induced with pGlu-Abeta3-42, produce high concentrations of immunoglobulin G antibodies that react with the toxic protein deposits. The authors say the antibodies generated by ACI-24 cover a broader range of binding sites on target proteins than earlier immunotherapy candidates for Alzheimer’s disease targeting amyloid-beta, or Abeta.

AC Immune is developing ACI-24 as a treatment for individuals in early or mild stages of Alzheimer’s disease. In this study, the company used an optimized formulation of ACI-24. An earlier form of the vaccine is in early- and mid-stage clinical trials, evaluating ACI-24 among Alzheimer’s disease, or AD, patients in general and people also with Down syndrome, where as many as half of people with that condition develop dementia of some kind as they reach their 60s.

Andrea Pfeifer, AC Immune CEO and a co-author of the study, says in a company statement the findings are encouraging “because of the robust polyclonal immune response, including high concentrations of antibodies against highly neurotoxic pyroGlu-Abeta variants, which are thought to be key drivers of early AD. These neurotoxic pyroGlu-Abeta species are not strongly targeted by competing anti-Abeta vaccines.”

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