Alzheimer's Disease vaccine shows potential in pre-clinical studies

Published: 6-Jul-2016

Study team's approach has been licensed to Capo Therapeutics


Researchers at The Institute of Molecular Medicine in Huntington Beach, CA, with collaborators at the University of California at Irvine, CA and at Flinders University in Adelaide, Australia claim to have created a unique vaccine formulation and approach to Alzheimer's Disease (AD).

AD is the most common cause of dementia. Immunotherapeutic strategies targeting two proteins, B-amyloid (AB) and tau, have displayed strong disease-modulating effects in animal models of AD, leading to attempts by industry to use anti-AB or anti-tau therapeutics in clinical trials. But the majority of active vaccines targeting AB pathology have failed in clinical trials probably because they were not initiated as early as possible in people who are at risk of AD, they are prodromal, or have mild AD, and they were not successful at inducing therapeutically potent concentrations of anti-AB antibodies.

The research team, whose study results are published in the Nature Publishing Group journal of Scientific Reports, used several steps to optimise their approach and overcome traditional setbacks. First, they decided to target B cell antigenic epitopes from AB and tau proteins that are found in the disease state. These were then fused to a universal vaccine platform based on a string of Th foreign epitopes, called Multi-TEP. Next, an insulin-based adjuvant was added and the team concluded that an optimal AD vaccine formulation, adjuvant selection and targeting of the right pathological molecules at the right stage of disease would be crucial to a successful immunotherapeutic approach.

No other studies have achieved the level of effective antibody titres we have achieved so I am excited to take this into the clinic

Their approach yielded very high therapeutic titres of anti-AB and anti-tau antibodies as well as inducing powerful cellular immune responses in animal models. The antibodies generated bound strongly to brain tissue from AD cases indicating the therapeutic potential of these antibodies. Immune sera from animals vaccinated with both anti-tau and anti-AB vaccines, or with a dual vaccine targeting both pathological molecules, recognised AB and tau simultaneously in human brains from AD cases. This approach may be especially beneficial in the elderly because the vaccine uses memory T cells that are in abundance in elderly patients instead of relying on activation of naive T cells, which decline with age, the researchers said.

'This study suggests that we can immunise patients with early stages of AD with our anti-AB vaccine and, if it progresses, then vaccinate with our anti-tau vaccine,' says Dr Michael Agadjanyan, Professor and Head of Immunology at the Institute for Molecular Medicine and faculty at the Institute for Memory Impairments and Neurological Disorders, UCI, and one of the senior authors of the study. 'No other studies have achieved the level of effective antibody titres we have achieved so I am excited to take this into the clinic. It is a completely novel approach.'

The composition of matter, formulation and methods of use have been submitted to the US patent office and have been exclusively licensed to Capo Therapeutics, a company started to commercialise this approach.

You may also like