Alzheimer’s Vaccine

The main focus of Capo Therapeutics is the development of an effective and safe vaccine against Alzheimer’s Disease (AD), one of the most devastating diseases of the century. Amyloid-beta (Ab) immunotherapy is considered to be a promising approach to reducing the level of Ab in the CNS of AD patients. However, data from the first clinical trial AN1792 indicated that vaccine should be designed not to induce autoreactive cellular responses and to be effective in the majority of the individuals from the risk groups.

Therefore, we are focused on the generation of peptide (Petrushina I. et al., 2007  ) or DNA based (Movsesyan N. et al., 2008Movsesyan N. et al., 2008) epitope vaccines composed of self B cell epitope of Ab peptide and foreign universal T cell epitopes such as synthetic Pan DR epitope PADRE or epitopes from currently approved conventional vaccines. Based on our research the protein AD vaccine was developed and will be tested in clinical trials in the nearest future. On the other hand, together with our collaborators at UCI MIND we generated a DNA-based epitope vaccine composed of 3 copies of self B cell epitope, foreign T cell epitope PADRE and macrophage derived chemokine (MDC) (Movsesyan N. et al., 2008). We demonstrated that immunization of 3xTg-AD mice with DNA epitope vaccine:

  • Induced high titers of anti-Ab antibody production without activation of autoreactive T cells
  • Reduced soluble and insoluble Ab accumulation in brains of vaccinated mice
  • Improved cognitive performance
  • Reduced glial activation without inducing hemorrhages

Currently the safety and efficacy of a DNA AD epitope vaccine is being tested in monkeys using the TDS-IM electroporation system in collaboration with ICHOR Medical Systems. DNA vaccines exhibit several significant advantages when compared to recombinant protein or peptide-based vaccines and are very effective in mice. However, they traditionally induce low immune responses in large animals and humans. Therefore, the translation of a DNA vaccine to the clinic may require further enhancement of immunogenicity using different approaches. Currently we are working on the further enhancement of the immunogenicity of our DNA epitope vaccine by:

  • Improving the DNA delivery system
  • Developing more effective immunization protocols such as the prime/boost regimen
  • Combining DNA immunization with an immunostimulant patches (in collaboration with Intercell)
  • Incorporating additional foreign Th cell epitopes to target pre-existing memory T cells

Collectively, our published and unpublished results generated with our collaborators demonstrated that a DNA- and protein- based epitope vaccines could be a translatable and effective vaccine strategy for the prevention and treatment of AD.

Selected publications