Vaccines Against Alzheimer's Disease (AD)

As a chronic neurodegenerative disease, Alzheimer's disease is slowly aggravated over time. Most of the patients are older than 65 years old, in addition to worse and worse memory, with disease advancing, language problems, and disorientation will also seriously impair the quality of life and even be life-threatening. These situations raise the need to develop effective AD vaccines. Creative Biolabs is a pioneer in the field of vaccine research. We have also conducted in-depth exploration and research on AD vaccines, and have a wealth of successful experience.

Alzheimer's Disease (AD)

Synapse – Creative Biolabs

Alzheimer's disease (AD) is age-related dementia and is the most common form of neurodegenerative disease. It is estimated that 46 million people worldwide are suffering from AD, and the number is still rising. At present, there is no clear conclusion about the cause of AD and various hypotheses are trying to clarify the cause of the disease. These hypotheses include the genetic heritability hypothesis, cholinergic hypothesis, amyloid hypothesis, tau hypothesis, and neurovascular hypothesis, which considers the weakening of the blood-brain barrier function as the cause. There is evidence that the human immune system is capable of producing protective natural antibodies with the ability to recognize and remove abnormal forms of proteins that cause AD. The immune surveillance mechanism will weaken as it ages, and AD will occur when this effect compromises an increasing number of abnormal proteins associated with AD.

Relevant Immunogens in AD

The immune system has a natural protective immunity that recognizes, neutralizes, and removes aberrant form of AD-related proteins. Currently, more and more recognized AD-related immunogen proteins are Amyloid β (Aβ), Tau, and α-Synuclein. The typical characteristic of the two isoforms Aβ40, Aβ42 of Aβ is the ability to form amyloids and lead to misfolding. Soluble Aβ has synaptic toxicity, which can cause the disruption of receptor, destroying the signal pathway and eventually leading to synaptic damage and memory impairment. The role of the tau protein is to stabilize the microtubule assembly of neurons. The normal function of this protein requires phosphorylation. Aβ isolated in the brain of patients with late-onset AD can induce hyperphosphorylation of tau, thus vaccines containing phosphorylated tau may be effective in preventing AD. α-synuclein interacts with lipids in the cell membrane and may synergize with Aβ and tau to accelerate neuronal degeneration in AD. It has also been reported that α-synuclein fibrils interacts with tau and inhibits its function and promotes its accumulation, which in turn leads to the dysfunction of neurons.

Development of Vaccines for AD

Brain damage in AD patients is irreversible, and the patient's immune system is weakened by aging, so prophylactic AD vaccines may be more beneficial than therapeutic. Clinical studies have demonstrated the protective effect of natural antibodies against neurotoxic Ab oligomers, which can slow the decline in cognitive function in patients with prodromal AD. However, in terms of vaccines, based on amyloid cascade hypothesis, vaccines targeting the amyloid-β (Aβ) amino-terminal region that are effective in the AD transgenic mouse model have not shown efficacy in humans. Two promising strategies for developing AD vaccines today are subunit vaccines and DNA vaccines.

Subunit Vaccines for AD

The key components of the AD subunit vaccine are antigens and adjuvants, similar to subunit vaccines for viruses or cancer. The immune response that viral or cancer vaccine needs to trigger should have the ability to kill cells that carry foreign surface antigens. Those antigens are often short linear T cell epitopes, while the antigens of AD vaccines are self-antigens, which are different from the normal form due to misfolding thus belonging to the conformational epitopes. Such conformational epitopes include B and T cell epitopes, which makes their use as antigens more complex, as a damaging Th1 autoimmune response may be induced. In the study of AN1792 AD vaccine, a similar phenomenon was also observed. Therefore, the current efforts are to use only B cell epitopes of Aβ, combined with Th1 or Th2 adjuvants, but the results are not satisfactory, and even complications have occurred. In addition, due to the emergence of evidence for synergy between Aβ and tau, bivalent vaccines using these two proteins as immunogens are also a strategy for the development of AD vaccines.

DNA Vaccines for AD

The use of host cells to express AD-associated antigens by genetic vaccination is a promising AD vaccine strategy. A DNA vaccine containing a gene encoding the Aβ protein is capable of inducing a Th2 immune response against a toxic soluble oligomer, although the level of expression is lower and the corresponding high-affinity antibody level is also lower. Despite that DNA vaccines produce lower levels of antibodies than subunit vaccines, their selectivity for conformational epitopes is high.

Alzheimer's Disease not only seriously affects the quality of life of patients, but also becomes a burden on society. Creative Biolabs is committed to building a healthy and harmonious human society. Under the leadership of a team of professional scientists, Creative Biolabs has continued to overcome difficulties and has accumulated a great deal of experience while serving a wide range of research partners. These have further enhanced our service capabilities and quality. We have advanced technology and rich experience in AD vaccine development. If you have any needs in this area, please do not hesitate to contact us!

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