Modified Tetanus Vaccine Could Protect Against Alzheimer’s

Combining the tetanus vaccine with a viral particle that normally affects cucumbers can be used to treat psoriasis and allergies, and may even protect against Alzheimer’s disease, research from the Universities of Dundee and Oxford has demonstrated.

The vaccine showed positive results in models of psoriasis and cat allergy and was shown to raise antibody levels thought to be beneficial in Alzheimer’s disease. These vaccines can be either preventative, which is the hope for Alzheimer’s but also therapeutic, meaning they can cure a disease like psoriasis after it has already been established.

Scientists led by Dundee’s Dr John Foerster and Oxford’s Professor Martin Bachmann, were able to take the protein coat of cucumber mosaic virus and incorporate a tetanus vaccine-derived protein structure known to stimulate the immune system in order to create vaccines to treat multiple chronic diseases.

Blocking Proteins

More research is required to test the efficacy of the therapeutic in a clinical setting, but the study opens up the possibility of hundreds of thousands of people being spared the ravages of chronic diseases.

“As an academic dermatologist with special interest in the immune system,” Dr Foerster said, “my specific attention is on vaccines to be developed against chronic skin diseases. The idea is pretty simple – for diseases such as psoriasis or eczema, the newest and most effective medicines on the market are so-called ‘antibodies’, which are what you and I produce against bugs in a common cold.

For chronic diseases, these antibodies are specially made against one of the body’s own proteins. By blocking that single protein, the disease gets better. To use the example of psoriasis, a protein called Interleukin 17 needs to be active for the disease to progress. By creating a vaccine that stimulates the body to make antibodies against Interleukin 17 itself we can replace the need for frequent and expensive injections and make this type of treatment much more affordable and accessible to patients who could otherwise not afford specially made antibodies.

Our research shows that this technique works in mice and, importantly, our new vaccine technology shows that it is likely to be a more effective type of vaccine than existing ones in older people. Since many patients with chronic conditions like psoriasis are elderly this technology may work much better to obtain effective vaccines.”

Beta Amyloid Vaccine?

In Alzheimer’s, it is known that a protein called beta amyloid can cause brain damage resulting in inhibited function.

Previous unsuccessful trials saw patients injected directly with antibodies against the same target but the new research suggests that starting the treatment – in the form of prophylactic vaccines – could provide a way of offering treatment even before the disease becomes clinically apparent.

It is possible such prophylactic approach may work better and this could not be done using frequent antibody injections.

Structure resolution of engineered CMV VLPs by cryoEM

Structure resolution of engineered CMV VLPs by cryoEM.
VLPs were dissolved in borate-EDTA containing buffer, vitrified and analyzed by EM using a Tecnai F30 ‘Polara’ microscope (FEI)
a Representative 2-D view of vitrified VLP, generated from repeated imaging each field of view along the Z- axis creating a series of images (constituting a movie).
From ~300 movies, 6685 particles were selected for data processing.
b Examples of generated 2-D classification, 20 were generated based on average electron density. White bar corresponds to 50 nm. Cross sectional Selection refinement towards 3-D electron density model and an initial model fitting data to icosahedral symmetry produced 9 Å model.
c High level refinement further improved resolution to 4.2 Å.
In addition, d the internal view reveals ordered elements (shown in orange) are visible on the interior of the capsid shell.
e Resolution Fitting reconstruction reveals that the obtained structure corresponds to X-ray crystal structural data.
Credit: Andris Zeltins, et al. CC-BY

Professor Bachmann, Professor of Vaccinology at the Jenner Institute in Oxford, said,

“Alzheimer`s disease usually develops in elderly people. The fact that the vaccine described here is optimised for old individuals seems therefore particularly helpful. An additional important aspect of the current work is that we developed a platform technology and are currently broadening our preclinical studies to vaccines against Parkinson`s disease as well as chronic pain.”

The researchers are now looking to begin clinical testing of the vaccine and have already received regulatory approval to initiate testing in humans.

Present antibodies for psoriasis treatment typically need to be injected at least once a month to keep working, and cost around £10,000 per patient annually. A vaccine would offer much more affordable treatment.

Andris Zeltins, Jonathan West, Franziska Zabel, Aadil El Turabi, Ina Balke, Stefanie Haas, Melanie Maudrich, Federico Storni, Paul Engeroff, Gary T. Jennings, Abhay Kotecha, David I Stuart, John Foerster & Martin F. Bachmann
Incorporation of tetanus-epitope into virus-like particles achieves vaccine responses even in older recipients in models of psoriasis, Alzheimer’s and cat allergy
npj Vaccines 2, Article number: 30 (2017) doi:10.1038/s41541-017-0030-8

Image: Wellcome Images