Vaccine Inquiry

The development of Alzheimer’s vaccine primarily aims at two targets, amyloid beta (Aβ) and tau protein. Their accumulation during Alzheimer’s disease (AD) progression can cause neuronal damage. Therefore, researchers hope that the immune system is able to recognize the antigenic characteristics of the two proteins and produce antibodies against them.

However, current research indicates that almost all attempts to develop vaccines using Aβ end in disappointment, probably because the vaccine has the wrong immunogen, the B-cell epitope of Aβ, which stimulates an antibody response that releases the neurotoxic soluble Aβ oligomers trapped in plaque, and the use of proinflammatory adjuvants that induce a destructive inflammatory autoimmune response. Thus, the development of a safe and effective Alzheimer’s vaccine that induces protective antibody production requires new strategies, and lessons learned from past vaccine failures should be considered.

Strategies for Development of an Effective Alzheimer’s Vaccine

The presence of protective immunity against AD decreases with age, and therefore, AD vaccine development should focus on prevention.

• Protein immunogens: In the vaccine against AD, the immunogen is an autoantigen that differs from its normal form in its misfolding, resulting in an abnormal three-dimensional structure or conformational epitope, with unique associative properties, leading to the formation of cytotoxic oligomers. Thus, an ideal AD vaccine immunogen should have stable conformational epitope characteristics of neurotoxic oligomers to selectively induce protective immunity against these oligomers. Due to the synergistic effect between Aβ and tau protein, an effective preventive vaccine should be considered with both Aβ and tau immunogens.
• Adjuvant: Adjuvant is also a key component for vaccines development. Low acute toxicity and a good margin of safety are necessary conditions for vaccine adjuvants. One requirement that is essential for an effective AD vaccine is to stimulate Th2 immunity alone because Aβ and tau can induce proinflammatory Th1 immunity that exacerbates AD, and microglia upon phagocytosis of Aβ produces inflammatory cytokines and other inflammatory mediators. Therefore, AD vaccine should have a sole Th2 adjuvant. An additional complication of AD vaccination is immunosenescence, which leads to an immune decline associated with aging. Thus, an effective adjuvant should ameliorate immunosenescence in addition to inducing a sole Th2 and inhibiting Th1 immunity.
• Genetic vaccine: In addition to subunit vaccines, genetic immunization is another promising approach to AD vaccines, in which the immunogen is expressed by host cells that have been transfected with a gene encoding for the whole or part of a protein. Although the level of antibodies induced by DNA vaccines do not approach those obtained with subunit vaccines, the selectivity of conformational epitopes is high.

About Alzheimacy

As an advanced technology company in the field of life science, Alzheimacy has the comprehensive strength of all-around basic research and preclinical research of AD vaccine development. Combining traditional and state-of-the-art genetic engineering techniques, we hope to address urgent and unmet medical needs through the efficient production of highly immunogenic vaccines.

• Basic Research

Research on the pathogenesis of AD is challenging, but it can provide us with the right direction for the effective development of AD therapies. Alzheimacy’s researchers are engaged in studies on the pathogenesis of AD and hope to provide more comprehensive insights into the discovery of novel protein immunogens, epitope identification and characterization, protein conformation analysis, protein expression, protein interactions analysis, etc., to address the unique challenges faced along the way.

• Pre-clinical Development

Our professional technical team consists of experts from different fields of expertise, relying on our expert team, we are able to complete every step of the way from vaccine design to target validation to preclinical assessment. At Alzheimacy, we have established an integrated technology platform for vaccine development, covering various technologies related to molecular biology, biochemistry, structural biology, immunology, and built an animal model research platform, including transgenic animals that carry the mutant human genes responsible for AD. Not only do we perform advanced vaccine design, formulation optimization (such as adjuvant selection and delivery system selection), we also have vaccine analytical testing programs (including but not limited in identity tests, purity tests, microbial tests, potency tests and stability tests) and a comprehensive list of in vitro and in vivo preclinical assessment to evaluate the safety, potency and quality of candidate AD vaccines. In addition, we can offer advice on process development and we also partner with multiple commercial cGMP facilities for large-scale vaccine production.

Alzheimacy has the ability to participate in Alzheimer’s vaccine development launched by pharmaceutical and biotechnology companies and leading academic institutions. With the increased demand for AD therapeutics development, we hope to grow with our partners.