Our immune system’s capacity to mount a well-regulated defense against foreign substances, including toxins, weakens with age and makes vaccines less effective in people over age 65.
At the same time, research has shown that immunotherapy targeting neurotoxic forms of the peptide amyloid beta (oligomeric Aβ) may halt the progression of Alzheimer’s disease, the most common age-related neurodegenerative disease.
In a new study, researchers found that an antigen-presenting dendritic vaccine with a specific antibody response to oligomeric Aβ may be safer and offer clinical benefit in treating Alzheimer’s disease.
The vaccine, called E22W42 DC, uses immune cells known as dendritic cells (DC) loaded with a modified Aβ peptide as the antigen.
The research was conducted by a team at the University of South Florida Health (USF Health).
One of the two hallmark pathologies of Alzheimer’s disease is hardened deposits of Aβ that clump together between nerve cells (amyloid protein plaques) in the brain; the other is neurofibrillary tangles of tau protein inside brain cells.
Both lead to damaged neurological cell signaling, ultimately causing the onset of Alzheimer’s disease and symptoms.
Unfortunately, clinical trials of all anti-amyloid treatments for Alzheimer’s disease so far have failed—including the initial vaccine trial targeting Aβ (AN-1792), which was suspended in 2002 after several immunized patients developed central nervous system inflammation.
A next-generation anti-amyloid vaccine for Alzheimer’s would ideally produce long-lasting, moderate antibody levels needed to prevent Aβ oligomers from further aggregating into destructive Alzheimer’s plaques, without over-stimulating the immune systems of elderly people.
In this study, the researchers tested the vaccine they formulated using modified Aβ-sensitized dendritic cells derived from mouse bone marrow.
The study included three groups of transgenic mice genetically engineered to develop high levels of Aβ and behavioral/cognitive abnormalities that mimic human Alzheimer’s disease.
The team found the vaccine slowed memory impairment in the Alzheimer’s transgenic mice.
In a cognitive test, the vaccinated mice also showed much less errors in working memory than the mice injected with control vaccines.
Loss of working memory makes it difficult to learn and retain new information, a characteristic of Alzheimer’s disease.
The vaccinated mice also showed higher levels of anti-Aβ antibodies in both in their brains and in their blood than the transgenic control mice.
The team says a major advantage of E22W42 is that the antigen can stimulate a specific T-cell response that activates the immune system and silence some T-cell epitopes associated with an autoimmune response.
Though the E22W42-sensitized DC vaccine is being developed for patients with Alzheimer’s disease, it can potentially help strengthen the immune system of elderly patients (with other age-related disorders) as well.
One author of the study is Chuanhai Cao, Ph.D.
The study is published in the Journal of Alzheimer’s Disease.
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