Dementia vaccine
The ability of the human immune system to provide regulated protection against foreign substances weakens with age. That is why any vaccines are less effective in people over 65 years of age. At the same time, studies show that immunotherapy aimed at neurotoxic forms of beta-amyloid protein (oligomeric Aß) can stop the progression of Alzheimer's disease, the most common neurodegenerative disease.
A group of researchers led by Chuanhai Cao from the University of South Florida focused their efforts on overcoming excessive inflammation and other complications that hinder the development of a vaccine against Alzheimer's disease in people with weakened immunity.
Preclinical research shows that an antigen-presenting dendritic vaccine with a specific antibody response to oligomeric Aß may be safer and have clinical efficacy in the treatment of Alzheimer's disease. The E22W42 DC vaccine contains dendritic cells (DC) loaded with a modified Aß protein as an antigen.
There are two characteristic links in the development of Alzheimer's disease – these are solid deposits of Aß (amyloid plaques) that accumulate between nerve cells in the brain, and neurofibrillary tangles of tau protein inside brain cells. Both lead to disruption of signal transmission between neurons, and, ultimately, to the development of clinical symptoms of Alzheimer's disease.
A new therapeutic vaccine uses the body's own immune cells to target toxic Aß molecules. And, importantly, it has a strong immunomodulatory effect without causing unwanted autoimmune reactions in aging mice.
Unfortunately, clinical trials of anti-amyloid drugs for the treatment of Alzheimer's disease have so far failed, including trials of one vaccine targeting Aß (AN-1792), which were suspended in 2002 after several immunized patients developed inflammation of the central nervous system. Inflammation is the primary symptom of Alzheimer's disease, so the development of inflammation as a side effect essentially adds fuel to the fire.
In this study, the team tested a new vaccine with modified Aß-sensitized dendritic cells obtained from the bone marrow of mice. Dendritic cells in the body interact with other immune cells (T- and B-lymphocytes) to help regulate immunity, including suppressing unwanted reactions to healthy tissues.
In other words, this vaccine can coordinate both innate and acquired immunity to potentially overcome age-related immune system disorders.
The study included three groups of transgenic (APP/PS1) mice genetically modified to express large amounts of Aß and develop behavioral/cognitive abnormalities that mimic Alzheimer's disease in humans. One group was vaccinated with the studied E22W42 DC vaccine, the other was injected with endogenous beta-amyloid to stimulate dendritic cells (wild-type vaccine group), and the third group was injected with dendritic cells that did not contain the Aß protein (DC control group). The fourth group consisted of untreated healthy old mice (nontransgenic control group).
The vaccine slowed memory deterioration in transgenic mice with Alzheimer's disease, while mice vaccinated with E22W42 DC showed memory similar to the characteristics of non-transgenic untreated mice. In the cognitive memory matrix test (water maze with radial sleeve), mice vaccinated with E22W42 DC also showed significantly fewer errors than mice injected with only unsensitized dendritic cells (DC control). Loss of working memory makes it difficult to assimilate and memorize new information, this is characteristic of Alzheimer's disease.
There were no significant differences in the amount of inflammatory cytokines in the plasma of vaccinated mice compared to control mice. The researchers concluded that the E22W42 DC vaccine does not have much potential to overstrain the immune system.
In addition, E22W42 DC-vaccinated mice showed higher levels of antibodies against Aß both in the brain and in the blood than in transgenic control mice injected with dendritic cells that did not contain the modified Aß protein.
The researchers concluded that only Aß proteins with mutations introduced into the T-cell epitope (the area of the antigen surface where complementary antibodies bind) can sensitize dendritic cells to target toxic oligomeric forms of Aß. The main advantage of E22W42 DC is that its antigen can stimulate a specific T-cell response that activates the immune system and silences some T-cell epitopes associated with the autoimmune response.
That is, the sensitized E22W42 DC vaccine, although developed for patients with Alzheimer's disease, is potentially able to strengthen the immune system of elderly patients with other age-related disorders.
The University of South Florida has received a patent for the E22W42 DC vaccine technology.
Article G.Song et al. An Immunomodulatory Therapeutic Vaccine Targeting Oligomeric Amyloid-β is published in the Journal of Alzheimer's Disease.
Aminat Adzhieva, portal "Eternal Youth" http://vechnayamolodost.ru based on EurekAlert materials: New anti-AB vaccine could help halt Alzheimer's progression, preclinical study finds.